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Sample records for 4-nqo dmba-epoxide icr-170

  1. EFFECT OF pH ON THE MUTAGENIC POTENCY OF ICR-170 IN THE REPRODUCTIVE GLANDS OF FEMALE SCHISTOSOMA JAPONICUM%PH对ICR-170诱变日本血吸虫雌虫生殖腺的影响

    Institute of Scientific and Technical Information of China (English)

    蒋守富; 潘彩娥; 陆钦淹

    2003-01-01

    目的探讨溶液pH对诱变剂ICR-170诱变日本血吸虫雌虫生殖腺的影响程度.方法用5种pH值(pH 7.2-8.0)的ICR-170溶液处理日本血吸虫尾蚴30 min或45 min后,经皮肤接种小鼠观察雌虫诱变率和成虫回收率.结果溶液pH值对ICR-170的诱变作用影响较大,诱变率随着溶液pH值的上升而下降.10μg/ml 45 min组和15μg/ml 30 min组在pH 7.2时的雌虫诱变率分别为pH 7.8时的13倍和6倍,当pH>7.4时,2种浓度的ICR-170引起的诱变率基本接近.溶液pH值对于成虫回收率的影响程度远低于对诱变率的影响程度.结论在诱变日本血吸虫雌虫生殖腺时,ICR-170具有较强的pH依赖型特性.

  2. Anticarcinogenesis effect of Gynura procumbens (Lour Merr on tongue carcinogenesis in 4NQO-induced rat

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    D. Agustina

    2006-09-01

    Full Text Available In Indonesia Gynura procumbens (Lour Merr leaves have been long used as various cancers medication. Many in vitro and in vivo studies have demonstrated anticarcinogenesis of ethanol extract of Gynura procumbens leaves. The aim of this study was to investigate the anticarcinogenesis of the ethanol extract of Gynura procumbens leaves on 4 nitroquinoline 1-oxide (4NQO-induced rat tongue carcinogenesis. Fifty six 4 week old male Sprague Dawley rats were used in this study and divided into 7 groups. Group 1, 2 and 3 were lingually induced by 4NQO for 8 weeks. In groups 2 and 3 the extract was given simultaneously with or after 4NQO induction finished, each for 10 weeks and 26 weeks, respectively. Groups 4, 5 and 6 were induced by 4NQO for 16 weeks. However, in groups 5 and 6 the extract was given as well simultaneously with or after the 4NQO induction, each for 18 weeks, respectively. Group 7 served as the as untreated control group. The results from microscopical assessment showed that tongue squamous cell carcinomas (SCC developed in 100% (3/3 of group 1. However, only 33.3% (2/6 and 25% (2/8 of rats in groups 2 and 3, respectively demonstrated tongue SCC. Among groups 4, 5 and 6, no significant difference of tongue SCC incidence was observed. From these results it is apparent that the ethanol extract of Gynura procumbens leaves could inhibit the progression of 4NQOinduced rat tongue carcinogenesis in the initiation phase.

  3. Apc-Mutant Kyoto Apc Delta (KAD Rats Are Susceptible to 4-NQO-Induced Tongue Carcinogenesis

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    Takuji Tanaka

    2014-07-01

    Full Text Available Despite widening interest in the possible association between infection/ inflammation and cancer development, knowledge of this issue in relation to oral cancer remains inadequate. This study aimed to determine the susceptibility of Apc-mutant Kyoto Apc Delta (KAD rats, which are vulnerable to developing inflammation-associated colorectal carcinogenesis, to 4-nitroquinoline 1-oxide (4-NQO-induced tongue carcinogenesis in order to clarify the role of inflammation in oral cancer. KAD (20 males and 22 females and F344/NS1c (22 males and 23 females rats received drinking water with or without 4-NQO (20 ppm for eight weeks. Histopathological and immunohistochemical analyses of the tongue were performed at week 20. Additionally, the mRNA expression of inflammatory cytokines in the tongue mucosa was determined at week 8. Tongue squamous cell carcinoma (SCC developed in the KAD and F344/NS1c rats that received 4-NQO. Regardless of gender, the incidence and multiplicity of tongue SCC were greater in the KAD rats than in the F344/NS1c rats. In addition, the multiplicity of tongue SCC in the female KAD rats was significantly greater than that observed in the male KAD (p < 0.01 and female F344/NS1c rats (p < 0.05. The levels of inflammation and the mRNA expression of inflammatory cytokines in the tongue in the 4-NQO-treated female KAD rats were the highest among the rats given 4-NQO. These results show that KAD rats, particularly females, are susceptible to 4-NQO-induced tongue carcinogenesis, suggesting the utility of models employing KAD rats for investigating the pathobiology of oral (tongue carcinogenesis associated with inflammation.

  4. Apc-Mutant Kyoto Apc Delta (KAD) Rats Are Susceptible to 4-NQO-Induced Tongue Carcinogenesis

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    Tanaka, Takuji, E-mail: tmntt08@gmail.com [Department of Diagnostic Pathology (DDP) & Research Center of Diagnostic Pathology (RC-DiP), Gifu Municipal Hospital, 7-1 Kashima-Cho, Gifu 500-8513 (Japan); Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan); Shimizu, Masahito; Kochi, Takahiro; Shirakami, Yohei [Department of Internal Medicine/Gastroenterology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan); Mori, Takayuki [Department of Pharmacy, Ogaki Municipal Hospital, 4-86 Minaminokawa-cho, Ogaki 503-8502 (Japan); Watanabe, Naoki [Department of Diagnostic Pathology (DDP) & Research Center of Diagnostic Pathology (RC-DiP), Gifu Municipal Hospital, 7-1 Kashima-Cho, Gifu 500-8513 (Japan); Naiki, Takafumi [Department of Clinical Laboratory, Gifu Municipal Hospital, 7-1 Kashima-cho, Gifu 500-8513 (Japan); Moriwaki, Hisataka [Department of Internal Medicine/Gastroenterology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan); Yoshimi, Kazuto; Serikawa, Tadao; Kuramoto, Takashi [The Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501 (Japan)

    2014-07-21

    Despite widening interest in the possible association between infection/inflammation and cancer development, knowledge of this issue in relation to oral cancer remains inadequate. This study aimed to determine the susceptibility of Apc-mutant Kyoto Apc Delta (KAD) rats, which are vulnerable to developing inflammation-associated colorectal carcinogenesis, to 4-nitroquinoline 1-oxide (4-NQO)-induced tongue carcinogenesis in order to clarify the role of inflammation in oral cancer. KAD (20 males and 22 females) and F344/NS1c (22 males and 23 females) rats received drinking water with or without 4-NQO (20 ppm) for eight weeks. Histopathological and immunohistochemical analyses of the tongue were performed at week 20. Additionally, the mRNA expression of inflammatory cytokines in the tongue mucosa was determined at week 8. Tongue squamous cell carcinoma (SCC) developed in the KAD and F344/NS1c rats that received 4-NQO. Regardless of gender, the incidence and multiplicity of tongue SCC were greater in the KAD rats than in the F344/NS1c rats. In addition, the multiplicity of tongue SCC in the female KAD rats was significantly greater than that observed in the male KAD (p < 0.01) and female F344/NS1c rats (p < 0.05). The levels of inflammation and the mRNA expression of inflammatory cytokines in the tongue in the 4-NQO-treated female KAD rats were the highest among the rats given 4-NQO. These results show that KAD rats, particularly females, are susceptible to 4-NQO-induced tongue carcinogenesis, suggesting the utility of models employing KAD rats for investigating the pathobiology of oral (tongue) carcinogenesis associated with inflammation.

  5. The antimutagenic effect of monoterpenes against UV-irradiation-, 4NQO- and t-BOOH-induced mutagenesis in coli

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    Nikolić Biljana

    2011-01-01

    Full Text Available The aim of this work was to investigate the antimutagenic potential of monoterpenes from sage and basil in Escherichia coli. The mutagenic potential of monoterpenes was pre-screened with Salmonella/microsome reversion assay in strain TA100 and no mutagenic effect was detected. The antimutagenic potential against UV- 4NQO- and t-BOOH induced mutagenesis was evaluated in E. coli K12 and E. coli WP2 by reversion assays. The obtained results indicate that camphor and thujone reduce UV- and 4NQO-induced mutations; myrcene reduces t-BOOH-induced mutations, while eucalyptol and linalool reduce mutagenicity by all tested mutagens. Considering evolutionary conservation of DNA repair and antioxidative protection, the obtained results indicate that further antigenotoxicity studies should be undertaken in eukaryotes.

  6. The effect of vitamin C on the hamster cheek pouch treated with the water soluble carcinogen 4-nitroquinoline-1-oxide (4NQO).

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    Kandarkar, S V; Sawant, S S

    1996-07-01

    Vitamin C is an essential nutrient whose protective influence is carcinogenesis has been reported frequently, suggesting that vitamin C inhibits the formation of some carcinogens and decreases the incidence and delays of the neoplastic lesions. However, the mechanisms by which this occurs are unknown. In this study, the water soluble carcinogen 4-nitroquinoline-1-oxide (4NQO) has been used to induce a high yield of tumours in the oral cavity either singly or in combination with tobacco. Since the mucosa of rats is less susceptible to carcinogens than the hamster cheek pouch, the hamster cheek pouch has been used to study the influence of vitamin C on 4NQO-induced oral malignancy. The aim of this study was to determine whether topically applied vitamin C had an effect on the oral carcinogenesis induced by application of 4NQO. Similarly, an attempt was made to study the modulating effect of vitamin C on the histopathological and ultrastructural changes during the neoplastic process in the hamster. Vitamin C appeared to delay tumour induction and had other protective effects against neoplasia. PMID:8776418

  7. Development of a 4-NQO toxic equivalency factor (TEF) approach to enable a preliminary risk assessment of unknown genotoxic compounds detected by the Ames II test in UV/H2O2 water treatment samples

    NARCIS (Netherlands)

    Martijn, A.J.; Rompay, van A.R.; Penders, E.J.M.; Alharbi, Y.; Baggelaar, P.; Kruithof, J.C.; Rietjens, I.M.C.M.

    2016-01-01

    An approach to enable a preliminary risk assessment of unknown genotoxic compounds formed by MP UV/H2O2 treatment of nitrate rich water, is described. Since the identity and concentration of specific genotoxic compounds is not established yet, a compound specific risk assessment cannot be performed.

  8. Study of synergistic DNA-damaging effects of low-intensity 2450 MHz microwave and 4-nitroquinoline on human lymphocytes in vitro

    International Nuclear Information System (INIS)

    Objective: To study the synergistic DNA-damaging effects of low-intensity 2450 MHz micro-wave (MW, 5.0 mW/cm2) and 4-nitroquinoline (4-NQO) on human lymphocytes. Methods: The DNA damages of human lymphocytes treated with microwave and 4-NQO were detected using the comet assay. Three combination-exposure ways of MW and 4-NQO were used: MW irradiation before 4-NQO exposure (MW+4-NQO), simultaneous exposure to MW and 4-NQO(MW-4-NQO), and MW irradiation after 4-NQO exposure (4-NQO+MW). Results: The differences of DNA-damage indexes (comet tail length, comet shape and total comet length) between MW group and control group were not significant (P>0.05).When the dose of 4-NQO was 50 μmol/L or 25 μmol/L, the differences of DNA-damage indexes between MW+4-NQO group and corresponding 4-NQO group were significant (P0.05). Conclusion: Low-intensity 2450 MHz microwave does not induce DNA-damage directly, but could enhance the DNA-damaging effects induced by 4-NQO when human lymphocytes have been treated with MW irradiation before 4-NQO exposure

  9. Combination of bexarotene and the retinoid CD1530 reduces murine oral-cavity carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide

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    Tang, Xiao-Han; Osei-Sarfo, Kwame; Urvalek, Alison M.; Zhang, Tuo; Scognamiglio, Theresa; Gudas, Lorraine J.

    2014-01-01

    We investigated the effects of bexarotene (a retinoid X receptor agonist), CD1530 (a retinoic acid receptor γ selective agonist), and the combination of these two drugs for the prevention of oral carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide (4-NQO) in a mouse model of human oral-cavity and esophageal squamous-cell carcinoma previously generated in our laboratory. We observed decreased numbers of neoplastic tongue lesions and reduced lesion severity in the 4-NQO plus CD1530 (4N+C) and 4-NQO plus bexarotene plus CD1530 (4N+B+C) groups compared with the 4-NQO group. RNA-Seq analyses showed increases in transcripts in cell proliferation/cell cycle progression pathways in the 4-NQO vs. the untreated group. In addition, β-catenin and matrix metallopeptidase 9 (MMP9) protein levels and reactive oxygen species (ROS), as assessed by 4-hydroxynonenal (4-HNE) staining, were elevated in tongue tissues 17 wk after the termination of the 4-NQO treatment. The 4N+B, 4N+C, and 4N+B+C groups showed dramatically lower levels of β-catenin, MMP9, and 4-HNE staining compared with the 4-NQO group. The major reduction in 4-HNE staining in the retinoid treatment groups suggests a novel mechanism of action, reduction of ROS, by which bexarotene and CD1530 inhibit carcinogenesis. PMID:24927566

  10. In-vivo Antioxidant Effects of Ethyl Acetate Fraction of Mentha spicata L. on 4-Nitroquinoline-1-Oxide Injected Mice

    OpenAIRE

    Arumugam, Ponnan; Ramesh, Arabandi

    2011-01-01

    Antioxidant effects of ethyl acetate fraction of Mentha spicata (L.) were evaluated against 4-nitroquinoline-1-oxide injected mice. For this study, experiment setup consisted of 36 albino mice of either sex divided into 6 groups: Control (25% DMSO in water), ethyl acetate fraction (EAF) alone group (80, 160 mg/Kg body weight-bwt), 4-NQO (7.5 mg/Kg bwt-IP) alone and 4-NQO + EAF. EAF and vehicles were administered orally for five consecutive days. 4-NQO (7.5 mg/Kg bwt) was injected intraperiton...

  11. Modulatory Effects of Mentha spicata (Linn. against 4 Nitroquinoline-1- Oxide Induced Chromosome Damage and Oxidative Stress in Mice

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    Ponnan Arumugam

    2015-12-01

    Full Text Available Mentha spicata is a common medicinal and edible plant in India and used in the ayurvedic system of medicine to treat various ailments including as a memory enhancer. The present study is aimed to evaluate the modulatory effects of Mentha spicata (Linn. against 4?nitroquinoline- 1-oxide (4-NQO induced chromosome damage and oxidative stress in mice. Experiments were conducted with eight groups of either sex of mice. Ethanol extract (EE of three doses (80, 160 and 320 mg/kg body weight-bw with or without 4-NQO along with vehicle control (25% DMSO in water were administered orally for five consecutive days. 4-NQO (7.5 mg/kg bw was injected intraperitoneally on the sixth day, and the animals scarified the following day. 4-NQO enhanced the frequency of micronucleated polychromatic erythrocytes (MnPCEs by about 4.2 times the control value, 15.78 MnPCEs/2500 PCEs. Pretreatment with EE, significantly reduced the MnPCEs frequency (50-69% induced by 4-NQO. Moreover, 4-NQO enhanced the lipid peroxidation (LPO by about 60% with decrease of enzymatic antioxidants in the range 27-41% and 38-60% for nonenzymatic antioxidants over the respective controls. Pre-treatment with the EE, brought down 4-NQO induced LPO significantly with in a dose dependent manner. All the measured antioxidants are positively modulated by the EE. The modulated values at high doses are either comparable with the controls or even higher than the control values.

  12. Protective effects of solvent fractions of Mentha spicata (L. leaves evaluated on 4-nitroquinoline-1-oxide induced chromosome damage and apoptosis in mouse bone marrow cells

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    Ponnan Arumugam

    2009-01-01

    Full Text Available Spearmint leaves (Mentha spicata L. contain high levels of antioxidants that are known to protect against both exogenous and endogenous DNA damage. In this study, the protective effects of the hexane fraction (HF, chloroform fraction (CF and ethyl acetate fraction (EAF in an ethanol extract from M. spicata were evaluated against 4-nitroquinoline-1-oxide (4-NQO induced chromosome damage and apoptosis in bone marrow cells of Swiss albino mice. Two (EAF; 80 and 160 mg/ kg body weight - bw or three (HF and CF; 80, 160 and 320 mg/ kg bw doses of solvent fractions or vehicle control (25% DMSO in water were administered orally for five consecutive days. Upon the sixth day, 4-NQO was injected intraperitoneally. The animals were killed the following day. Other control groups were comprised of animals treated with either the vehicle control or the various doses of solvent fractions, but with no 4-NQO treatment. 4-NQO induced micro-nucleated polychromatic erythrocytes (MnPCEs in all the test groups. However, pre-treatment of animals with the solvent fractions significantly reduced the 4-NQO-induced MnPCEs as well as the percentage of apoptotic cells. The reduction of both MnPCE and apoptosis was more evident following the pre-treatment of animals with 160 mg/kg bw EAF.

  13. Protective effects of solvent fractions of Mentha spicata (L.) leaves evaluated on 4-nitroquinoline-1-oxide induced chromosome damage and apoptosis in mouse bone marrow cells.

    Science.gov (United States)

    Arumugam, Ponnan; Ramesh, Arabandi

    2009-10-01

    Spearmint leaves (Mentha spicata L.) contain high levels of antioxidants that are known to protect against both exogenous and endogenous DNA damage. In this study, the protective effects of the hexane fraction (HF), chloroform fraction (CF) and ethyl acetate fraction (EAF) in an ethanol extract from M. spicata were evaluated against 4-nitroquinoline-1-oxide (4-NQO) induced chromosome damage and apoptosis in bone marrow cells of Swiss albino mice. Two (EAF; 80 and 160 mg/ kg body weight - bw) or three (HF and CF; 80, 160 and 320 mg/ kg bw) doses of solvent fractions or vehicle control (25% DMSO in water) were administered orally for five consecutive days. Upon the sixth day, 4-NQO was injected intraperitoneally. The animals were killed the following day. Other control groups were comprised of animals treated with either the vehicle control or the various doses of solvent fractions, but with no 4-NQO treatment. 4-NQO induced micro-nucleated polychromatic erythrocytes (MnPCEs) in all the test groups. However, pre-treatment of animals with the solvent fractions significantly reduced the 4-NQO-induced MnPCEs as well as the percentage of apoptotic cells. The reduction of both MnPCE and apoptosis was more evident following the pre-treatment of animals with 160 mg/kg bw EAF. PMID:21637463

  14. In-vivo Antioxidant Effects of Ethyl Acetate Fraction of Mentha spicata L. on 4-Nitroquinoline-1-Oxide Injected Mice.

    Science.gov (United States)

    Arumugam, Ponnan; Ramesh, Arabandi

    2011-01-01

    Antioxidant effects of ethyl acetate fraction of Mentha spicata (L.) were evaluated against 4-nitroquinoline-1-oxide injected mice. For this study, experiment setup consisted of 36 albino mice of either sex divided into 6 groups: Control (25% DMSO in water), ethyl acetate fraction (EAF) alone group (80, 160 mg/Kg body weight-bwt), 4-NQO (7.5 mg/Kg bwt-IP) alone and 4-NQO + EAF. EAF and vehicles were administered orally for five consecutive days. 4-NQO (7.5 mg/Kg bwt) was injected intraperitoneally on the 6(th) day. After 24 h, the animals were killed; liver sample was extracted and used for bio-assay. 4-NQO alone treated group decreased (27-60%) the antioxidant activities and promoted lipid peroxidation (LPO-60%) over their respective control values. Pretreatment with EAF, at the maximum dose (160 mg/Kg bwt) brought down the LPO up to 87% enhanced by 4-NQO. Among the enzymatic antioxidants, glutathione S-transferase (GST) was the most affected enzyme with 4-NQO and the least was catalase (CAT). Pretreatment with EAF (160 mg/Kg bwt), the restoration of antioxidants like glutathione peroxidase, superoxide dismutase, and CAT were found equal or less than 1.2 fold higher than that of the respective control values whereas, GST was observed to be the most restored antioxidant. Be reduced glutathione (GSH) and the least vitamin C over their control values. EAF restored the GSH and Vitamin E levels were found to be 1.2 fold higher than the respective control values. PMID:24250414

  15. Antigenotoxic properties of Terminalia arjuna bark extracts.

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    Scassellati-Sforzolini, G; Villarini, L M; Moretti, L M; Marcarelli, L M; Pasquini, R; Fatigoni, C; Kaur, L S; Kumar, S; Grover, I S

    1999-01-01

    Compounds possessing antimutagenic properties (polyphenols, tannins, vitamins, etc.) have been identified in fruits, vegetables, spices, and medicinal plants. Terminalia arjuna (Combretaceae), a tropical woody tree occurring throughout India and known locally as Kumbuk, is a medicinal plant rich in tannins and triterpenes that is used extensively in Ayurvedic medicine as a cardiac tonic. The aim of the present collaborative work was to test six solvent extracts from the bark of Terminalia arjuna for antigenotoxic activity using in vitro short-term tests. Terminalia arjuna extracts were obtained by sequential extraction using acetone, methanol, methanol + HCl, chloroform, ethyl acetate, and ethyl ether. The antigenotoxic properties of these extracts were investigated by assessing the inhibition of genotoxicity of the directacting mutagen 4-nitroquinoline-N-oxide (4NQO) using the "comet" assay and the micronucleus (MN) test. Human peripheral blood leukocytes were incubated with different concentrations of the six extracts (from 5 to 100 microg/ mL) and with 4NQO (1 and 2 microg/mL, for the "comet" assay and MN test, respectively). Each extract/4NQO combination was tested twice; in each experiment, positive control (4NQO alone) and negative control (1% DMSO) were set. "Comet" assay results showed that acetone and methanol extracts were highly effective in reducing the DNA damage caused by 4NQO, whereas the acidic methanol, chloroform, ethyl acetate, and ethyl ether extracts showed less marked or no antigenotoxic activity. In the MN test, a decrease in 4NQO genotoxicity was observed by testing this mutagen in the presence of acetone, methanol, chloroform, and ethyl acetate extracts, even though the extent of inhibition was not always statistically significant. PMID:15281223

  16. 4-nitroquinoline-1-oxide-induced mutagen sensitivity and risk of cutaneous melanoma: a case-control analysis.

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    Wang, Li-E; Li, Chunying; Xiong, Ping; Gershenwald, Jeffrey E; Prieto, Victor G; Duvic, Madeleine; Lee, Jeffrey E; Grimm, Elizabeth A; Hsu, Tao C; Wei, Qingyi

    2016-04-01

    Mutagen sensitivity assay, which measures the enhanced cellular response to DNA damage induced in vitro by mutagens/carcinogens, has been used in the study of cancer susceptibility. 4-Nitroquinoline-1-oxide (4-NQO), an ultraviolet (UV) radiation-mimetic chemical, can produce chromosomal breaks in mammalian cells and induce cancer. Given the potential role of 4-NQO as the experimental mutagen substituting for UV as the etiological carcinogen of cutaneous melanoma (CM), we tested the hypothesis that cellular sensitivity to 4-NQO is associated with the risk of developing CM in a case-control study of 133 patients with primary CM and 176 cancer-free controls. Short-term blood cultures were treated with 4-NQO at a final concentration of 10 μmol/l for 24 h and scored chromatid breaks in 50 well-spread metaphases. Multivariate logistic regression was used to calculate odds ratios and 95% confidence intervals. We found that the log-transformed frequency of chromatid breaks was significantly higher in 133 patients than in 176 controls (P=0.004) and was associated with an increased risk for CM (adjusted odds ratio=1.78, 95% confidence interval: 1.12-2.84) after adjustment for age and sex. Moreover, as the chromatid break values increased, the risk for CM increased in a dose-dependent manner (P(trend)=0.003). Further analysis explored a multiplicative interaction between the sensitivity to 4-NQO and a family history of skin cancer (P(interaction)=0.004) on the risk of CM. Therefore, our findings suggest that sensitivity to 4-NQO may be a risk factor for the risk of CM, which is more sensitive than UV-induced chromotid breaks.

  17. Identification of Ethanol and 4-Nitroquinoline-1-Oxide Induced Epigenetic and Oxidative Stress Markers During Oral Cavity Carcinogenesis

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    Urvalek, Alison M.; Osei-Sarfo, Kwame; Tang, Xiao-Han; Zhang, Tuo; Scognamiglio, Theresa; Gudas, Lorraine J.

    2015-01-01

    Background Head and neck squamous cell carcinoma (HNSCC) is a cancer that is characterized by its high morbidity and mortality rates. While tobacco use and alcohol consumption are two major contributing factors for HNSCC carcinogenesis, how the combination of tobacco and alcohol increases HNSCC risk is not understood. Methods We combined the 4-nitroquinoline-1-oxide (4-NQO) oral carcinogenesis and Meadows-Cook alcohol mouse models to elucidate the molecular events and to identify novel biomarkers associated with oral cancer development. Results By genome-wide RNA-seq of tongue samples (three mice per group) we identified changes in transcripts that mediate alcohol metabolism and oxidative stress (Aldh2, Aldh1a3, Adh1, Adh7, and Cyp2a5) in mice treated with 4-NQO followed by ethanol (4-NQO/EtOH) as compared to the vehicle control/untreated samples (V.C./Untr.). We measured major, global increases in specific histone acetylation and methylation epigenetic marks (H3K27ac, H3K9/14ac, H3K27me3, and H3K9me3) in the oral cavities of V.C./EtOH, 4-NQO/Untr. and 4-NQO/EtOH treatment groups compared to the V.C./Untr. group. We detected changes in histone epigenetic marks near regulatory regions of genes involved in ethanol metabolism by chromatin immunoprecipitation (ChIP). For instance, the Aldh2 promoter showed increased H3K27me3 marks, and Aldh2 mRNA levels were reduced by 10-fold in 4NQO/EtOH vs. V.C./Untr. tongue samples. 4-NQO/EtOH treatment also caused increases in markers of oxidative stress, including 4-HNE, MCT4/Slc16a3, and TOM20, as measured by immunohistochemistry. Conclusions We delineate a mechanism by which 4-NQO and ethanol can regulate gene expression during the development of HNSCC, and suggest that histone epigenetic marks and oxidative stress markers could be novel biomarkers and targets for the prevention of HNSCC. PMID:26207766

  18. Starre konfokale Laser Scanning Endoskopie zur Frühdiagnostik des Oropharynxkarzinoms - eine tierexperimentelle Studie

    OpenAIRE

    Farahati, B; Stachs, O.; Prall, F; Kramp, B; Just, T; Pau, HW

    2009-01-01

    Einleitung: Ziel der tierexperimentellen Untersuchungen ist es, die für die HNO-Heilkunde neue Technologie, die starre konfokale Endoskopie (SKE), auf einen möglichen Einsatz zur Diagnostik von präneoplastischen Schleimhautveränderungen zu prüfen. Methoden: Die Tumorinduktion im Tiermodell wurde mit einem wasserlöslichen Quinolin-Derivat vorgenommen (4-NQO). Insgesamt 50 Mäuse (C57Bl/6) erhielten das chemische Kanzerogen 4-NQO über das Trinkwasser über einem Zeitraum von 8 bis 18 Woch...

  19. HPLC和SOS显色反应检测不同微生物脱除4-NQO基因毒性能力%Determination of Antigenotoxic Activity of Different Probiotic Microorganisms against 4-Nitroquino-line-l-oxide (4-NQO) by SOS Chromotest and HPLC

    Institute of Scientific and Technical Information of China (English)

    胡明臣; 任发政; 王芳; 张明; 邱芳萍

    2011-01-01

    SOS chromotest and HPLC were used for determining the antigenotoxic activity of 36 probiotic strains against 4-NQO. Meanwhile, their ability to remove 4-NQO genotoxicity was comparatively analyzed by HPLC. One L. plantarum strain, 5 Bifidobacterium strains, L. casei strain Shirota, 3 Bacillus strains, 2 yeast strains, 7 Lsalivarius strains and I Lactobacillus bulgaricus strain were found to have a higher ability to remove 4-NQO genotoxicity among these strains. No significant difference in removal ability for 4-NQO genotoxicity was observed among strains from the same genus. Only L.salivarius strains could produce Px, suggesting the species-specific removal ability of probiotics for 4-NQO genotoxicity. Also, we found that the capability of converting 4-NQO into 4-HAQO decided the ability of probiotics to remove 4-NQO genotoxicity. This study can provide references and supports for further studies of the removal mechanism of 4-NQO genotoxicity by probiotics.%应用高效液相色谱法(high performance liquid chromatography, HPLC)和SOS显色反应测定36株益生菌脱除4-硝基喹啉-i-氧化物(4-NQO)基因毒性的能力,同时用HPLC对它们的图谱进行比较分析。研究发现,基因毒性清除率高的菌株有1株植物乳杆菌、5株双歧杆菌、干酪乳杆菌代田株、3株芽孢杆菌、2株酵母菌、7株唾液乳杆菌和一株保加利亚乳杆菌。同属于一个菌属的各个菌株基因毒性清除率之间差异不显著。图谱分析发现,只有唾液乳杆菌才产生P1,即益生菌脱除4-NQO基因毒性具有菌株特异性。研究还发现益生菌转化4-NQO为4-HAQO的能力是决定益生菌脱除4-NQO基因毒性能力大小的关键。

  20. Identification and dissection of a complex DNA repair sensitivity phenotype in Baker's yeast.

    Directory of Open Access Journals (Sweden)

    Ann Demogines

    2008-07-01

    Full Text Available Complex traits typically involve the contribution of multiple gene variants. In this study, we took advantage of a high-density genotyping analysis of the BY (S288c and RM strains of Saccharomyces cerevisiae and of 123 derived spore progeny to identify the genetic loci that underlie a complex DNA repair sensitivity phenotype. This was accomplished by screening hybrid yeast progeny for sensitivity to a variety of DNA damaging agents. Both the BY and RM strains are resistant to the ultraviolet light-mimetic agent 4-nitroquinoline 1-oxide (4-NQO; however, hybrid progeny from a BYxRM cross displayed varying sensitivities to the drug. We mapped a major quantitative trait locus (QTL, RAD5, and identified the exact polymorphism within this locus responsible for 4-NQO sensitivity. By using a backcrossing strategy along with array-assisted bulk segregant analysis, we identified one other locus, MKT1, and a QTL on Chromosome VII that also link to the hybrid 4-NQO-sensitive phenotype but confer more minor effects. This work suggests an additive model for sensitivity to 4-NQO and provides a strategy for mapping both major and minor QTL that confer background-specific phenotypes. It also provides tools for understanding the effect of genetic background on sensitivity to genotoxic agents.

  1. CHARACTERIZATION OF A RAT ORAL SQUAMOUS-CELL CARCINOMA CELL-LINE UHG-RAC-'93 INDUCED BY 4-NITROQUINOLINE-1-OXIDE IN-VIVO

    NARCIS (Netherlands)

    WITJES, M; SCHOLMA, J; VANDRUNEN, E; ROODENBURG, JLN; MESANDER, G; HAGEMEIJER, A; TOMSON, AM

    1995-01-01

    This study describes several characteristics of a cell line, UHG-RaC '93 derived from rat oral squamous cell carcinoma induced by the carcinogen 4-nitroquinoline-1-oxide (4NQO), The cell Line was established from explant cultures without support of fibroblast feeder cells and continued for > 30 pass

  2. 4-nitroquinoline-1-oxide induced experimental oral carcinogenesis.

    Science.gov (United States)

    Kanojia, Deepak; Vaidya, Milind M

    2006-08-01

    Human oral cancer is the sixth largest group of malignancies worldwide and single largest group of malignancies in the Indian subcontinent. Seventy percent of premalignant cancers appear from premalignant lesions. Only 8-10% of these lesions finally turn into malignancy. The appearance of these premalignant lesions is one distinct feature of human oral cancer. At present there is dearth of biomarkers to identify which of these lesions will turn into malignancy. Regional lymph node metastasis and locoregional recurrence are the major factors responsible for the limited survival of patients with oral cancer. Paucity of early diagnostic and prognostic markers is one of the contributory factors for higher mortality rates. Cancer is a multistep process and because of constrain in availability of human tissues from multiple stages of oral carcinogenesis including normal tissues, animal models are being widely used, aiming for the development of diagnostic and prognostic markers. A number of chemical carcinogens like coal tar, 20 methyl cholanthrene (20MC), 9,10-dimethyl-1,2-benzanthracene (DMBA) and 4-nitroquinoline-1-oxide (4NQO) have been used in experimental oral carcinogenesis. However, 4NQO is the preferred carcinogen apart from DMBA in the development of experimental oral carcinogenesis. 4NQO is a water soluble carcinogen, which induces tumors predominantly in the oral cavity. It produces all the stages of oral carcinogenesis and several lines of evidences suggest that similar histological as well as molecular changes are observed in the human system. In the present review an attempt has been made to collate the information available on mechanisms of action of 4NQO, studies carried out for the development of biomarkers and chemopreventives agents using 4NQO animal models. PMID:16448841

  3. Use of high frequency ultrasound to monitor cervical lymph node alterations in mice.

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    Elyse L Walk

    Full Text Available Cervical lymph node evaluation by clinical ultrasound is a non-invasive procedure used in diagnosing nodal status, and when combined with fine-needle aspiration cytology (FNAC, provides an effective method to assess nodal pathologies. Development of high-frequency ultrasound (HF US allows real-time monitoring of lymph node alterations in animal models. While HF US is frequently used in animal models of tumor biology, use of HF US for studying cervical lymph nodes alterations associated with murine models of head and neck cancer, or any other model of lymphadenopathy, is lacking. Here we utilize HF US to monitor cervical lymph nodes changes in mice following exposure to the oral cancer-inducing carcinogen 4-nitroquinoline-1-oxide (4-NQO and in mice with systemic autoimmunity. 4-NQO induces tumors within the mouse oral cavity as early as 19 wks that recapitulate HNSCC. Monitoring of cervical (mandibular lymph nodes by gray scale and power Doppler sonography revealed changes in lymph node size eight weeks after 4-NQO treatment, prior to tumor formation. 4-NQO causes changes in cervical node blood flow resulting from oral tumor progression. Histological evaluation indicated that the early 4-NQO induced changes in lymph node volume were due to specific hyperproliferation of T-cell enriched zones in the paracortex. We also show that HF US can be used to perform image-guided fine needle aspirate (FNA biopsies on mice with enlarged mandibular lymph nodes due to genetic mutation of Fas ligand (Fasl. Collectively these studies indicate that HF US is an effective technique for the non-invasive study of cervical lymph node alterations in live mouse models of oral cancer and other mouse models containing cervical lymphadenopathy.

  4. Use of high frequency ultrasound to monitor cervical lymph node alterations in mice.

    Science.gov (United States)

    Walk, Elyse L; McLaughlin, Sarah; Coad, James; Weed, Scott A

    2014-01-01

    Cervical lymph node evaluation by clinical ultrasound is a non-invasive procedure used in diagnosing nodal status, and when combined with fine-needle aspiration cytology (FNAC), provides an effective method to assess nodal pathologies. Development of high-frequency ultrasound (HF US) allows real-time monitoring of lymph node alterations in animal models. While HF US is frequently used in animal models of tumor biology, use of HF US for studying cervical lymph nodes alterations associated with murine models of head and neck cancer, or any other model of lymphadenopathy, is lacking. Here we utilize HF US to monitor cervical lymph nodes changes in mice following exposure to the oral cancer-inducing carcinogen 4-nitroquinoline-1-oxide (4-NQO) and in mice with systemic autoimmunity. 4-NQO induces tumors within the mouse oral cavity as early as 19 wks that recapitulate HNSCC. Monitoring of cervical (mandibular) lymph nodes by gray scale and power Doppler sonography revealed changes in lymph node size eight weeks after 4-NQO treatment, prior to tumor formation. 4-NQO causes changes in cervical node blood flow resulting from oral tumor progression. Histological evaluation indicated that the early 4-NQO induced changes in lymph node volume were due to specific hyperproliferation of T-cell enriched zones in the paracortex. We also show that HF US can be used to perform image-guided fine needle aspirate (FNA) biopsies on mice with enlarged mandibular lymph nodes due to genetic mutation of Fas ligand (Fasl). Collectively these studies indicate that HF US is an effective technique for the non-invasive study of cervical lymph node alterations in live mouse models of oral cancer and other mouse models containing cervical lymphadenopathy. PMID:24955984

  5. Characterization of hybrids between bovine (MDBK) and mouse (L-cell) cell lines.

    Science.gov (United States)

    Chinchar, V G; Floyd, A D; Chinchar, G D; Taylor, M W

    1979-02-01

    Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)-deficient mutants of a bovine kidney cell line (MDBK) were selected following mutagenesis with ethylmethane sulfonate or ICR-170G. MDBK mutants were hybridized to thymidine kinase-deficient L cells and selected in HAT medium. Parental and hybrid cells were characterized for isozyme patterns of lactic dehydrogenase malate dehydrogenase, glucose-6-phosphate dehydrogenase, and glutamate oxalate transaminase. Chromosomes of MDBK can be distinguished from mouse L cells by configuration and by fluorescent staining with Hoechst 33-258 stain. Hybrid cells contained both MDBK and L-cell chromosomes and had elevated DNA content. MDBK cells are normally restrictive for mengovirus replication. Both permissive and restrictive hybrids were found. Our data indicate that there was preferential loss of MDBK chromosomes in the hybrid cell lines.

  6. Xeroderma pigmentosum groups C and F

    International Nuclear Information System (INIS)

    The differential bead-labelling method for heterodikaryon complementation enabled us to allocate xeroderma pigmentosum patients XP40KO and XP38KO to complementation groups C and F, respectively. Group C XP40KO cells exhibited 15 % UDS and the 5 and 1.5-fold hypersensitivities to UV and 4-nitroquinoline-1-oxide (4NQO) killings, respectively, while group F XP38KO cells showed a higher residual level of 20 - 25 % UDS and a less UV/4NQO hypersensitivity than did the previously assigned group F strains. We reviewed the thus far assigned Japanese groups C and F subjects for the repair and clinical characteristics. The present group C XP40KO was typical, while XP38KO was heterogrnous within group F with respect to repair. (author)

  7. Effects of long-term administration of cancer-promoting substances on oral subepithelial mast cells in the rat.

    Science.gov (United States)

    Sand, L; Hilliges, M; Larsson, P A; Wallstrom, M; Hirsch, J M

    2002-01-01

    The role of oral subepithelial mast cells in the defence against tumours is a matter of controversy. The effect of established and suggested carcinogens, such as the carcinogen 4-nitroquinoline-N-oxide (4-NQO) and Herpes simplex virus type 1 (HSV-1), in combination with oral snuff on lower lip subepithelial mast cells (MC) was studied in rats. The rats were exposed to prolonged use of oral snuff. The test substances were administered in a surgically created canal in the lower lip of the rats. There were 15 rats in each test group and 10 rats in the control group. The amount of countable subepithelial mast cells decreased significantly when the rat oral mucosa was exposed to the oral carcinogen 4-NQO but the effect of oral snuff and HSV-1 infection was weak. Our findings suggest that mast cells play a role in immunological cell defence against chemical carcinogens. Further studies are needed to clarify the mechanisms. PMID:12529973

  8. Evaluation of the co-genotoxic effects of 1800 MHz GSM radiofrequency exposure and a chemical mutagen in cultured human cells

    Science.gov (United States)

    Perrin, Anne; Freire, Maëlle; Bachelet, Christine; Collin, Alice; Levêque, Philippe; Pla, Simon; Debouzy, Jean-Claude

    2010-11-01

    We investigated the effect of a 1800 MHz radiofrequency GSM signal combined with a known chemical mutagen (4-nitroquinoline-N-oxide: 4NQO) on human THP1 cells. Comet and γ-H2AX assays were used to assess DNA damage. No heating of the cell cultures was noted during exposure (2 h). The exposure of cells to electromagnetic fields with SARs of 2 to 16 W/kg did not increase the DNA damage induced by 4NQO, whereas the number of DNA strand breaks increased with a temperature increase of at least 4 °C. In conclusion, no co-genotoxic effect of radiofrequency was found at levels of exposure that did not induce heating.

  9. Modulatory action of 2-deoxy-D-glucose on mitomycin C-and 4-nitroquinoline-1-oxide-induced genotoxicity in Swiss albino mice In vivo

    Directory of Open Access Journals (Sweden)

    Mohapatra Rashmi

    2009-09-01

    Full Text Available Background: 2-Deoxy-D-glucose (2-DG, a structural analog of glucose is an effective inhibitor of glucose metabolism and ATP production. It selectively accumulates in cancer cells and interferes with glycolysis leading to cell death. 2-DG is shown to differentially enhance the radiation-induced damage in cancer cells both under euoxic and hypoxic conditions. A combination of 2-DG and ionizing radiation selectively destroys tumors while protecting the normal tissue. 2-DG is being advocated as an adjuvant in the radiotherapy and chemotherapy of cancer. Objective: The present investigation focuses on the modulatory effect of 2-DG on mitomycin C- (MMC and 4-nitroquinoline-1-oxide (4-NQO-induced cytogenetic damage in bone marrow cells of Swiss albino mice in vivo. Materials and Methods: Experimental animals were pretreated with 2-DG (500 mg/kg, i.p. for five consecutive days followed by MMC (2 mg/kg, i.p or 4-NQO (15 mg/kg, i.p., 24h prior to sacrifice. Control animals were given either the mixture of olive oil and acetone (3:1 or distilled water. Bone marrow cells were processed for the micronucleus assay and metaphase analysis for estimating cytogenetic damage. Results: 2-DG significantly (P < 0.001 reduced the frequency of aberrant cells induced by MMC (~90% and 4-NQO (~74%. Incidence of micronucleated polychromatic erythrocytes (MnPCEs induced by the mutagens were reduced up to 68%. Conclusion: 2-DG effectively reduces the MMC-and 4-NQO-induced genotoxicity.

  10. Protective effects of solvent fractions of Mentha spicata (L.) leaves evaluated on 4-nitroquinoline-1-oxide induced chromosome damage and apoptosis in mouse bone marrow cells

    OpenAIRE

    Ponnan Arumugam; Arabandi Ramesh

    2009-01-01

    Spearmint leaves (Mentha spicata L.) contain high levels of antioxidants that are known to protect against both exogenous and endogenous DNA damage. In this study, the protective effects of the hexane fraction (HF), chloroform fraction (CF) and ethyl acetate fraction (EAF) in an ethanol extract from M. spicata were evaluated against 4-nitroquinoline-1-oxide (4-NQO) induced chromosome damage and apoptosis in bone marrow cells of Swiss albino mice. Two (EAF; 80 and 160 mg/ kg body weight - bw) ...

  11. A novel role for DNA photolyase: binding to DNA damaged by drugs is associated with enhanced cytotoxicity in Saccharomyces cerevisiae.

    OpenAIRE

    Fox, M E; Feldman, B. J.; Chu, G.

    1994-01-01

    DNA photolyase binds to and repairs cyclobutane pyrimidine dimers induced by UV radiation. Here we demonstrate that in the yeast Saccharomyces cerevisiae, photolyase also binds to DNA damaged by the anticancer drugs cis-diamminedichloroplatinum (cis-DDP) and nitrogen mustard (HN2) and by the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Surprisingly, mutations in photolyase were associated with resistance of yeast cells to cis-DDP, MNNG, 4-nitroquinoline oxide (4NQO), and HN2....

  12. Estimates of DNA damage by the comet assay in the direct-developing frog Eleutherodactylus johnstonei (Anura, Eleutherodactylidae)

    OpenAIRE

    Laura Carolina Valencia; Adriana García; Martha Patricia Ramírez-Pinilla; Jorge Luis Fuentes

    2011-01-01

    The aim of this study was to use the Comet assay to assess genetic damage in the direct-developing frog Eleutherodactylus johnstonei. A DNA diffusion assay was used to evaluate the effectiveness of alkaline, enzymatic and alkaline/enzymatic treatments for lysing E. johnstonei blood cells and to determine the amount of DNA strand breakage associated with apoptosis and necrosis. Cell sensitivity to the mutagens bleomycin (BLM) and 4-nitro-quinoline-1-oxide (4NQO) was also assessed using the Com...

  13. Administration of a vaccine composed of dendritic cells pulsed with premalignant oral lesion lysate to mice bearing carcinogen-induced premalignant oral lesions stimulates a protective immune response

    OpenAIRE

    De Costa, Anna-Maria A.; Justis, Danielle N.; Schuyler, Corinne A.; M. Rita I. Young

    2012-01-01

    The use of dendritic cell (DC) vaccines as treatment for malignancy is complicated by immune evasion tactics often employed by carcinomas such as head and neck squamous cell carcinoma (HNSCC). The present study aims to determine if an immune response can be elicited by administering a DC vaccine during the premalignant stages of HNSCC, prior to development of immune escape. Mice treated with the carcinogen 4-nitroquinoline 1-oxide (4NQO) in drinking water develop premalignant oral lesions tha...

  14. STAT3 as a chemoprevention target in carcinogen-induced head and neck squamous cell carcinoma.

    OpenAIRE

    Peyser, ND; Wang, L.; Zeng, Y.; Acquafondata, M.; Freilino, ML; Li, H.; M. Sen; Gooding, WE; Satake, M; Wang, Z.; Johnson; Grandis, JR

    2016-01-01

    Head and neck squamous cell carcinoma (HNSCC) is a frequently fatal disease due in large part to a high rate of second primary tumor (SPT) formation. The 4-nitroquinoline 1-oxide (4-NQO) mouse model of oral carcinogenesis provides a robust system in which to study chemopreventive agents in the context of chemically-induced HNSCC tumors. Signal transducer and activator of transcription 3 (STAT3) is a potent oncogene that is hyperactivated by tyrosine phosphorylation early in HNSCC carcinogenes...

  15. Genotoxicity risk assessment of diversely substituted quinolines using the SOS chromotest.

    Science.gov (United States)

    Duran, Leidy Tatiana Díaz; Rincón, Nathalia Olivar; Galvis, Carlos Eduardo Puerto; Kouznetsov, Vladimir V; Lorenzo, Jorge Luis Fuentes

    2015-03-01

    Quinolines are aromatic nitrogen compounds with wide therapeutic potential to treat parasitic and microbial diseases. In this study, the genotoxicity of quinoline, 4-methylquinoline, 4-nitroquinoline-1-oxide (4-NQO), and diversely functionalized quinoline derivatives and the influence of the substituents (functional groups and/or atoms) on their genotoxicity were tested using the SOS chromotest. Quinoline derivatives that induce genotoxicity by the formation of an enamine epoxide structure did not induce the SOS response in Escherichia coli PQ37 cells, with the exception of 4-methylquinoline that was weakly genotoxic. The chemical nature of the substitution (C-5 to C-8: hydroxyl, nitro, methyl, isopropyl, chlorine, fluorine, and iodine atoms; C-2: phenyl and 3,4-methylenedioxyphenyl rings) of quinoline skeleton did not significantly modify compound genotoxicities; however, C-2 substitution with α-, β-, or γ-pyridinyl groups removed 4-methylquinoline genotoxicity. On the other hand, 4-NQO derivatives whose genotoxic mechanism involves reduction of the C-4 nitro group were strong inducers of the SOS response. Methyl and nitrophenyl substituents at C-2 of 4-NQO core affected the genotoxic potency of this molecule. The relevance of these results is discussed in relation to the potential use of the substituted quinolines. The work showed the sensitivity of SOS chromotest for studying structure-genotoxicity relationships and bioassay-guided quinoline synthesis.

  16. Topical polyethylene glycol as a novel chemopreventive agent for oral cancer via targeting of epidermal growth factor response.

    Directory of Open Access Journals (Sweden)

    Ramesh K Wali

    Full Text Available Head and neck squamous cell carcinoma (HNSCC is a major cause of morbidity and mortality underscoring the need for safe and effective chemopreventive strategies. Targeting epidermal growth factor receptor (EGFR is attractive in that it is an early critical event in HNSCC pathogenesis. However, current agents lack efficacy or have unacceptable toxicity. Several groups have demonstrated that the over-the-counter medication, polyethylene glycol (PEG has remarkable chemopreventive efficacy against colon carcinogenesis. Importantly, we reported that this effect is mediated through EGFR internalization/degradation. In the current study, we investigated the chemopreventive efficacy of this agent against HNSCC, using both the well validated animal model 4-NQO (4-nitroquinoline 1-oxide rat model and cell culture with the human HNSCC cell line SCC-25. We demonstrated that daily topical application of 10% PEG-8000 in the oral cavity (tongue and cavity wall post 4NQO initiation resulted in a significant reduction in tumor burden (both, tumor size and tumors/tumor bearing rat without any evidence of toxicity. Immunohistochemical studies depicted decreased proliferation (number of Ki67-positive cells and reduced expression of EGFR and its downstream effectors cyclin D1 in the tongue mucosa of 4NQO-rats treated with PEG. We showed that EGFR was also markedly downregulated in SCC-25 cells by PEG-8000 with a concomitant induction of G1-S phase cell-cycle arrest, which was potentially mediated through upregulated p21(cip1/waf1. In conclusion, we demonstrate, for the first time, that PEG has promising efficacy and safety as a chemopreventive efficacy against oral carcinogenesis.

  17. Lactobacillus salivarius REN inhibits rat oral cancer induced by 4-nitroquioline 1-oxide.

    Science.gov (United States)

    Zhang, Ming; Wang, Fang; Jiang, Lu; Liu, Ruihai; Zhang, Lian; Lei, Xingen; Li, Jiyou; Jiang, Jingli; Guo, Huiyuan; Fang, Bing; Zhao, Liang; Ren, Fazheng

    2013-07-01

    Despite significant advances in cancer therapy, cancer-related mobility and mortality are still rising. Alternative strategies such as cancer prevention thus become essential. Probiotics represent an emerging option for cancer prevention, but studies are limited to colon cancers. The efficiency of probiotics in the prevention of other cancers and the correlative mechanism remains to be explored. A novel probiotics Lactobacillus salivarius REN (L. salivarius REN) was isolated from centenarians at Bama of China, which showed highly potent antigenotoxicity in an initial assay. 4-nitroquioline 1-oxide (4NQO)-induced oral cancer model was introduced to study the anticancer activity of L. salivarius REN in vivo. The results indicated that oral administration of probiotic L. salivarius REN or its secretions could effectively suppress 4NQO-induced oral carcinogenesis in the initial and postinitial stage, and the inhibition was in a dose-dependent manner. A significant decrease of neoplasm incidence (65%-0%) was detected in rats fed with the high dose of L. salivarius REN [5 × 10(10) CFU/kg body weight (bw)/d]. In vivo evidences indicated that the probiotics inhibited 4NQO-induced oral cancer by protecting DNA against oxidative damage and downregulating COX-2 expression. L. salivarius REN treatment significantly decreased the expression of proliferating cell nuclear antigen (PCNA) and induced apoptosis in a dose-dependent manner. Our findings suggest that probiotics may act as potential agents for oral cancer prevention. This is the first report showing the inhibitory effect of the probiotics on oral carcinogenesis. PMID:23658366

  18. Ethanol Promotes Chemically Induced Oral Cancer in Mice through Activation of the 5-Lipoxygenase Pathway of Arachidonic Acid Metabolism

    Science.gov (United States)

    Guo, Yizhu; Wang, Xin; Zhang, Xinyan; Sun, Zheng; Chen, Xiaoxin

    2011-01-01

    Alcohol drinking is a known risk factor for oral cancer in humans. However, previous animal studies on the promoting effect of ethanol on oral carcinogenesis were inconclusive. It is necessary to develop an animal model with which the molecular mechanism of ethanol-related oral carcinogenesis may be elucidated in order to develop effective prevention strategies. In this study, mice were first treated with 4-nitroquinoline-1-oxide (4NQO, 100μg/ml in drinking water) for 8 weeks, and then given water or ethanol (8%) as the sole drink for another 16 weeks. During the experiment, 8% ethanol was well tolerated by mice. The incidence of squamous cell carcinoma (SCC) increased from 20% (8/41) to 43% (17/40; p<0.05). Expression of 5-lipoxygenase (5-Lox) and cyclooxygenase 2 (Cox-2) was increased in dysplasia and SCC of 4NQO-treated tongues, and further enhanced by ethanol. Using this mouse model, we further demonstrated that fewer cancers were induced in Alox5−/− mice, as were cell proliferation, inflammation, and angiogenesis in the tongue, as compared with Alox5+/+ mice. Interestingly, Cox-2 expression was induced by ethanol in knockout mice, while 5-Lox and leukotriene A4 hydrolase (LTA4H) expression and leukotriene B4 (LTB4) biosynthesis were dramatically reduced. Moreover, ethanol enhanced expression and nuclear localization of 5-Lox and stimulated LTB4 biosynthesis in human tongue SCC cells (SCC-15 and SCC-4) in vitro. In conclusion, this study clearly demonstrated that ethanol promoted 4NQO-induced oral carcinogenesis, at least in part, through further activation of the 5-Lox pathway of arachidonic acid metabolism. PMID:21881027

  19. Modulatory Effects of Mentha spicata (Linn.) against 4 Nitroquinoline-1- Oxide Induced Chromosome Damage and Oxidative Stress in Mice

    OpenAIRE

    Ponnan Arumugam; Siva Kamalakannan; Marudhamuthu Murugan

    2015-01-01

    Mentha spicata is a common medicinal and edible plant in India and used in the ayurvedic system of medicine to treat various ailments including as a memory enhancer. The present study is aimed to evaluate the modulatory effects of Mentha spicata (Linn.) against 4?nitroquinoline- 1-oxide (4-NQO) induced chromosome damage and oxidative stress in mice. Experiments were conducted with eight groups of either sex of mice. Ethanol extract (EE) of three doses (80, 160 and 320 mg/kg body weight-bw) wi...

  20. Evaluation of the SOS chromotest for the detection of antimutagens

    International Nuclear Information System (INIS)

    The SOS chromotest was applied for the detection of antimutagens. To raise SOS induction, the bacteria were treated with the mutagens, UV, 4-nitroquinoline N-oxide (4NQO), N-methyl-N'-nitro-N-nitroso-guanidine (MNNG), or benzo[a]pyrene (B[a]p). The inhibitory effects of L-ascorbic acid, glutathione, vanillin,5-fluorouracil (5-FU), 5-chlorouracil (5-CU), cobaltous chloride, sodium selenite and sodium arsenite, which are known as antimutagens, were investigated with their addition either simultaneously or post treatment time. In became clear that the SOS chromotest was very useful for the detection of antimutagens

  1. Initiation of esophageal squamous cell carcinoma (ESCC) in a murine 4-nitroquinoline-1-oxide and alcohol carcinogenesis model

    Science.gov (United States)

    Osei-Sarfo, Kwame; Scognamiglio, Theresa; Gudas, Lorraine J.

    2015-01-01

    Esophageal squamous cell carcinomas (ESCCs) are very common, aggressive tumors, and are often associated with alcohol and tobacco abuse. Because ESCCs exhibit high recurrence rates and are diagnosed at late stages, identification of prognostic and drug targets for prevention and treatment is critical. We used the 4-nitroquinoline-1-oxide (4-NQO) murine model of oral carcinogenesis and the Meadows-Cook model of alcohol abuse to assess changes in the expression of molecular markers during the initial stages of ESCC. Combining these two models, which mimic chronic alcohol and tobacco abuse in humans, we detected increased cellular proliferation (EGFR and Ki67 expression), increased canonical Wnt signaling and downstream elements (β-catenin, FoxM1, and S100a4 protein levels), changes in cellular adhesive properties (reduced E-cadherin in the basal layer of the esophageal epithelium), and increased levels of phosphorylated ERK1/2 and p38. Additionally, we found that treatment with ethanol alone increased the numbers of epithelial cells expressing solute carrier family 2 (facilitated glucose transporter, member 1) (SLC2A1) and carbonic anhydrase IX (CAIX), and increased the phosphorylation of p38. Thus, we identified both 4-NQO- and ethanol-specific targets in the initial stages of esophageal carcinogenesis, which should lead to the development of potential markers and therapeutic targets for human ESCC. PMID:25714027

  2. Antimutagenic activity of cashew apple (Anacardium occidentale Sapindales, Anacardiaceae fresh juice and processed juice (cajuína against methyl methanesulfonate, 4-nitroquinoline N-oxide and benzo[a]pyrene

    Directory of Open Access Journals (Sweden)

    Ana Amelia Melo-Cavalcante

    2008-01-01

    Full Text Available Cashew apple juice (CAJ, produced from the native Brazilian cashew tree (Anacardium occidentale, and has been reported to have antibacterial, antifungal, antitumor, antioxidant and antimutagenic properties. Both the fresh unprocessed juice and the processed juice (cajuína in Portuguese has been shown to consist of a complex mixture containing high concentrations of anacardic and ascorbic acids plus several carotenoids, phenolic compounds and metals. We assessed both types of juice for their antimutagenic properties against the direct mutagens methyl methanesulfonate (MMS and 4-nitroquinoline-N-oxide (4-NQO and the indirect mutagen benzo[a]pyrene (BaP using pre-treatment, co-treatment and post-treatment assays with Salmonella typhimurium strains TA100, TA102, and TA97a. In pre-treatment experiments with strains TA100 and TA102 the fresh juice showed high antimutagenic activity against MMS but, conversely, co-treatment with both juices enhanced MMS mutagenicity and there was an indication of toxicity in the post-treatment regime. In pre-, co-, and post-treatments with TA97a as test strain, antimutagenic effects were also observed against 4-NQO and BaP. These results suggest that both fresh and processed CAJ can protect the cells against mutagenesis induced by direct and indirect mutagens.

  3. Studying the synergistic damage effects induced by 1.8 GHz radiofrequency field radiation (RFR) with four chemical mutagens on human lymphocyte DNA using comet assay in vitro

    International Nuclear Information System (INIS)

    The aim of this investigation was to study the synergistic DNA damage effects in human lymphocytes induced by 1.8 GHz radiofrequency field radiation (RFR, SAR of 3 W/kg) with four chemical mutagens, i.e. mitomycin C (MMC, DNA crosslinker), bleomycin (BLM, radiomimetic agent), methyl methanesulfonate (MMS, alkylating agent), and 4-nitroquinoline-1-oxide (4NQO, UV-mimetic agent). The DNA damage of lymphocytes exposed to RFR and/or with chemical mutagens was detected at two incubation time (0 or 21 h) after treatment with comet assay in vitro. Three combinative exposure ways were used. Cells were exposed to RFR and chemical mutagens for 2 and 3 h, respectively. Tail length (TL) and tail moment (TM) were utilized as DNA damage indexes. The results showed no difference of DNA damage indexes between RFR group and control group at 0 and 21 h incubation after exposure (P > 0.05). There were significant difference of DNA damage indexes between MMC group and RFR + MMC co-exposure group at 0 and 21 h incubation after treatment (P 0.05). The experimental results indicated 1.8 GHz RFR (SAR, 3 W/kg) for 2 h did not induce the human lymphocyte DNA damage effects in vitro, but could enhance the human lymphocyte DNA damage effects induced by MMC and 4NQO. The synergistic DNA damage effects of 1.8 GHz RFR with BLM or MMS were not obvious

  4. Antimutagenicity of Methanolic Extracts from Anemopsis californica in Relation to Their Antioxidant Activity

    Directory of Open Access Journals (Sweden)

    Carmen Lizette Del-Toro-Sánchez

    2014-01-01

    Full Text Available Anemopsis californica has been used empirically to treat infectious diseases. However, there are no antimutagenic evaluation reports on this plant. The present study evaluated the antioxidant activity in relation to the mutagenic and antimutagenic activity properties of leaf (LME and stem (SME methanolic extracts of A. californica collected in the central Mexican state of Querétaro. Antioxidant properties and total phenols of extracts were evaluated using DPPH (1,1-diphenyl-2-picrylhydrazyl and Folin-Ciocalteu methods, respectively. Mutagenicity was evaluated using the Ames test employing Salmonella enterica serovar Typhimurium strains (TA98, TA100, and TA102, with and without an aroclor 1254 (S9 mixture. Antimutagenesis was performed against mutations induced on the Ames test with MNNG, 2AA, or 4NQO. SME presented the highest antioxidant capacity and total phenolic content. None of the extracts exhibited mutagenicity in the Ames test. The extracts produced a significant reduction in 2AA-induced mutations in S. typhimurium TA98. In both extracts, mutagenesis induced by 4NQO or methyl-N′-nitro-N-nitrosoguanidine (MNNG was reduced only if the exposure of strains was <10 μg/Petri dish. A. californca antioxidant properties and its capacity to reduce point mutations render it suitable to enhance medical cancer treatments. The significant effect against antimutagenic 2AA suggests that their consumption would provide protection against carcinogenic polycyclic aromatic compounds.

  5. Impact of Short-term 1,25-Dihydroxyvitamin D3 on the Chemopreventive Efficacy of Erlotinib against Oral Cancer.

    Science.gov (United States)

    Bothwell, Katelyn D; Shaurova, Tatiana; Merzianu, Mihai; Suresh, Amritha; Kuriakose, Moni A; Johnson, Candace S; Hershberger, Pamela A; Seshadri, Mukund

    2015-09-01

    Activation of the epidermal growth factor receptor (EGFR) pathway is an early event in head and neck carcinogenesis. As a result, targeting EGFR for chemoprevention of head and neck squamous cell carcinomas (HNSCC) has received considerable attention. In the present study, we examined the impact of 1,25(OH)2D3, the active metabolite of the nutritional supplement vitamin D on the chemopreventive efficacy of the EGFR inhibitor, erlotinib, against HNSCC. Experimental studies were conducted in patient-derived xenografts (PDX) and the 4-nitroquinoline-1-oxide (4NQO) carcinogen-induced model of HNSCC. Short-term treatment (4 weeks) of PDX-bearing mice with 1,25(OH)2D3 and erlotinib resulted in significant inhibition of tumor growth. Noninvasive MRI enabled longitudinal monitoring of disease progression in the 4NQO model with 100% of control animals showing evidence of neoplastic lesions by 24 weeks. Among the experimental groups, animals treated with the combination regimen showed the greatest reduction in tumor incidence and volume (P phospho-EGFR and phospho-Akt with the combination regimen. These results highlight the potential of 1,25(OH)2D3 to augment the efficacy of erlotinib against HNSCC. Further optimization of schedule and sequence of this combination regimen along with investigation into the activity of less calcemic analogues or dietary vitamin D is essential to fully realize the potential of this approach.

  6. Response of human epidermal keratinocytes to UV light

    International Nuclear Information System (INIS)

    This thesis presents a study on the response of human epidermal keratinocytes to UV light as well as to other agents like 4-NQO and TPA. The effects of ultraviolet (UV) light on the protein synthesis in cultured keratinocytes are presented in ch. III. The next chapter describes the construction of a cDNA library using mRNA isolated from UV irradiated kernatinocytes. This library was differentially screened with cDNA probes synthesized on mRNA from either UV irradiated or nonirradiated cells. Several groups of cDNA clones corresponding to transcripts whose level in the cytoplasm seem to be affected by exposure to UV light have been isolated and characterized by cross-hybridization, sequencing and Northern blot analysis. More detailed analysis of some of the cDNA clones is presented in the two chapters following ch. IV. The complete cDNA sequence of the proteinase inhibitor cystatin A and the modulation of its expression by UV light and the carcinogen 4-nitroquinoline 1-oxide (4-NQO) in keratinocytes are described in ch. V. Two other groups of cDNA clones have been isolated which do not cross-hybridize with each other on Southern blots. However, the primary structures of the proteins deduced from the nucleotide sequences of these two groups of cDNA clones are very similar. 212 refs.; 33 figs.; 2 tabs

  7. Deletion of macrophage migration inhibitory factor inhibits murine oral carcinogenesis: Potential role for chronic pro-inflammatory immune mediators.

    Science.gov (United States)

    Oghumu, Steve; Knobloch, Thomas J; Terrazas, Cesar; Varikuti, Sanjay; Ahn-Jarvis, Jennifer; Bollinger, Claire E; Iwenofu, Hans; Weghorst, Christopher M; Satoskar, Abhay R

    2016-09-15

    Oral cancer kills about 1 person every hour each day in the United States and is the sixth most prevalent cancer worldwide. The pro-inflammatory cytokine 'macrophage migration inhibitory factor' (MIF) has been shown to be expressed in oral cancer patients, yet its precise role in oral carcinogenesis is not clear. In this study, we examined the impact of global Mif deletion on the cellular and molecular process occurring during oral carcinogenesis using a well-established mouse model of oral cancer with the carcinogen 4-nitroquinoline-1-oxide (4NQO). C57BL/6 Wild-type (WT) and Mif knock-out mice were administered with 4NQO in drinking water for 16 weeks, then regular drinking water for 8 weeks. Mif knock-out mice displayed fewer oral tumor incidence and multiplicity, accompanied by a significant reduction in the expression of pro-inflammatory cytokines Il-1β, Tnf-α, chemokines Cxcl1, Cxcl6 and Ccl3 and other molecular biomarkers of oral carcinogenesis Mmp1 and Ptgs2. Further, systemic accumulation of myeloid-derived tumor promoting immune cells was inhibited in Mif knock-out mice. Our results demonstrate that genetic Mif deletion reduces the incidence and severity of oral carcinogenesis, by inhibiting the expression of chronic pro-inflammatory immune mediators. Thus, targeting MIF is a promising strategy for the prevention or therapy of oral cancer. PMID:27164411

  8. Ground water pollution by arsenic and its effects on health. Involvement of metabolic methylation in arsenic-induced genetic damage and tumorigenesis; Muki hiso no mechiru ka taisha to idenshi shogaisei narabini shuyo yuhatsusei

    Energy Technology Data Exchange (ETDEWEB)

    Yamanaka, K. [Nihon Univ., Tokyo (Japan)] Okada, S. [Shizuoka Prefecture (Japan)

    1997-07-10

    Drinking water contamination has become a worldwide problem. It is pointed out that re-evaluation of genetic damage with carcinogen is considered as an important problem particularly arsenic`s effects on health. To explain the genetic damage development mechanism of arsenic compound, results of the research conducted on the action of arsenic compound which develops during metabolic methylation process and inorganic arsenic are explained in this paper. The results of the study are summarized as follows. Arsenic genetic damage mutation is caused by dimethyl arsenic in main metabolism than inorganic arsenic. Lung DNA damage is induced by the interaction of O2 and arsenic peroxide radical. Dimethyl arsenic shows very important effect on lung cancer formation process which is induced based on 4-nitroquinoline-1-oxide (4NQO). It not only promotes lung cancer but it also plays an important role in malignant tumor`s mutation. 25 refs., 2 figs.

  9. 4NQO诱导大鼠腭黏膜癌模型建立的实验研究%A rat model of palatal mucosa carcinoma induced by 4-nitroquinolinel-oxide water solution

    Institute of Scientific and Technical Information of China (English)

    岳阳丽; 季旭东; 刘进忠

    2013-01-01

    目的:建立与人腭黏膜癌及癌前病变发生相似的动物模型.方法:体积分数为0.5%的四硝基喹啉-1-氧化物(4-nitroquinoline 1-oxide,4NQO)水溶液涂抹Wistar大鼠腭部黏膜至28周,肉眼及组织学观察癌变全过程.结果:随4NQO作用时间的延长,小鼠腭黏膜相继出现白色斑块、红白相间斑块、乳头状新生物和浸润性肿块等改变,组织学上经历了单纯性上皮增生、异常增生、原位癌、浸润性癌的病理过程,用药16、20、24、28周时腭癌的发生率分别为0、11.1%、44.4%、100%,未见远处转移.结论:4NQO涂抹法诱发大鼠腭癌模型建立方法简单、靶器官代表性强、病变典型,癌变时间稳定集中,且与人类口腔癌病变过程相似,是研究口腔癌的理想动物模型.%Aim:To establish a rat model for palatal mucosa carcinoma and precancerous lesions that is histologically and pathologically comparable to the human counterpart.Methods:0.5% 4NQO solution was applied to the rat's palate mucosa once two days,and the animals were observed until the 28th week.The rats were killed and their palatal mucosas were biopsied for pathological analyses.Results:Gross changes included leukoplakia,erythroplakia appearances,papillary hyperplasia and invasive carcinoma of the palatal mucosa of experimental group rats during carcinogenesis.The palate lesions had undergone a classical progress of squamous cell carcinoma including simple epithelial hyperplasia,dysplasia,in situ carcinoma and invasive cancer.The incidence of palate cancer in rats treated with 4NQO for 16 weeks,20 weeks,24 weeks,and 28 weeks was 0,11.1%,44.4% and 100%,respectively.No metastases were found.Conclusion:4NQO can reliably induce rat palatal preneoplastic lesions,carcinoma of the rat palatal mucosa.The process of carcinogenesis and the biological behavior parallel to those of human oral carcinoma.The target organ is typical,and the method is handy.This model is simple

  10. Investigation of the antimutagenic effects of selected South African medicinal plant extracts.

    Science.gov (United States)

    Verschaeve, L; Kestens, V; Taylor, J L S; Elgorashi, E E; Maes, A; Van Puyvelde, L; De Kimpe, N; Van Staden, J

    2004-02-01

    Dichloromethane extracts from different parts of Rhamnus prinoides, Ornithogalum longibracteatum, Gardenia volkensii, Spirostachys africana, Diospyros whyteana, Syzigium cordatum and Prunus africana were investigated for mutagenic and antimutagenic effects in Salmonella/microsome and micronucleus tests. None of the extracts tested in the Ames test were found to induce mutations or to modify the effect of the mutagen 4-nitroquinoline-oxide (4NQO). In the micronucleus test, extracts from twigs/bark of R. prinoides, twigs of D. whyteana, P. africana and S. cordatum significantly lowered the effect of the mutagen mitomycin C (MMC). Extracts from twigs/bark of G. volkensii and S. africana were genotoxic in the micronucleus test, while extracts of O. longibracteatum leaves potentiated the genotoxicity of MMC. This preliminary investigation shows that plant extracts used in traditional medicine may have particular effects with regard to mutagenicity and antimutagenicity indicating careful use in some instances and the need to isolate their active principles for further research.

  11. A pre-validation trial - testing genotoxicity of several chemicals using standard, medium- and high-throughput comet formats.

    Directory of Open Access Journals (Sweden)

    Kristine Bjerve Gutzkow

    2015-06-01

    Results obtained with the three systems (standard, medium- and high-throughput were essentially the same. The 96-minigel format was analysed with the fully automated scoring system IMSTAR and comparable results were achieved with the semi-automated scoring system from Perceptives. The known genotoxic chemicals MNU, B(aP, 4-NQO and cyclophosphamide showed little consistent sign of genotoxicity at concentrations causing limited cytotoxicity. D-mannitol and Triton X-100 were, as expected, non-genotoxic (though Triton X-100, at high concentrations, caused DNA breaks as an apparent secondary effect of cytotoxicity. Etoposide and bleomycin gave significant increase in DNA strand break at borderline cytotoxic concentrations. The limitation of the assay to detect damaged bases by known genotoxins may be overcome by incorporating a DNA repair enzyme, such as formamidopyrimidine-DNA-glycosylase (FPG, to convert damaged bases into breaks as shown by Azqueta A et al., Mutagenesis vol. 28 no. 3 pp. 271–277, 2013 .

  12. Evaluation of the Effect of Two Different Systemic Doses of Viola Odorata on Prevention of Induced Tongue Dysplasia in Rats

    Science.gov (United States)

    Helli, Sanaz; Damghani, Hossein; Mohajeri, Daryoush; Mesgari Abbasi, Mehran; Attaran, Rana; Zahed, Maryam

    2016-01-01

    Statement of the Problem Oral cancer is among the ten most common cancers worldwide. It affects the life quality of patients in many ways. Purpose The aim of this study was to compare the effects of two different systemic doses of Viola Odorata syrup on the prevention of 4-Nitroquinoline-1-oxide (4-NQO) induced tongue dysplasia in rats. Materials and Method Forty-eight male Wistar rats were divided into four groups of A, B, C and D. Group A served as the control group. The rats in groups B to D received 30 ppm of 4-NQO in drinking water for 12 weeks. Additionally, the rats in groups B and C received Viola Odorata syrup at doses of 15 and 5 ml/kg, respectively, 3 times a week. Body weights were measured three times a week. At the end, the rats were euthanized and the tongue was removed. Histological evaluations for carcinogenesis were carried out under a light microscope. Results The mean body weight of the rats in groups B, C, and D were lower than that in group A (p< 0.01). After 12 weeks of treatment, microscopically no histological changes of the tongue base epithelia were observed in the control group. The rats in group B did not show severe dysplastic changes; only mild to moderate histological changes including hyperplasia and hyperkeratosis were evident. These incidences were significantly more apparent in groups C with moderate to severe changes (p< 0.05) and group D with severe dysplastic changes (p< 0.01). Almost all rats in group D had hyperplasia and manifested all of the stages of dysplasia. Conclusion Viola Odorata extract has dose-dependent inhibitory effects on the development of tongue induced dysplasia. PMID:27602393

  13. A robust method for assessing chemically induced mutagenic effects in the oral cavity of transgenic Big Blue® rats.

    Science.gov (United States)

    Young, Robert R; Thompson, Chad M; Dinesdurage, Harshini R; Elbekai, Reem H; Suh, Mina; Rohr, Annette C; Proctor, Deborah M

    2015-08-01

    The Big Blue® (BB) in vivo mutation assay uses transgenic rodents to measure treatment-induced mutations in virtually any tissue. The BB assay can be conducted in rats or mice and is ideal for investigating tissue-specific mutagenic mode of action of tumor induction. Some tissues such as oral mucosa have not been thoroughly studied. Due to the small quantity and cartilaginous nature of oral cavity tissues, development of special prosection and DNA isolation methods was required to permit robust analysis of mutations in these tissues. Improved surgical methods permitted collection of adequate and reproducible quantities of tissue (∼45 mg gingiva/buccal and ∼30 mg gingiva/palate). Optimized DNA isolation methods included use of liquid nitrogen pulverization, homogenization, nuclei pelleting, digestion, and phenol/chloroform extraction, to yield sufficient quantities of DNA from these tissues. In preliminary optimization work, mutant frequency (MF) in tongue and gingiva was increased in rats exposed to the promutagen, benzo[a]pyrene, and the direct mutagen, N-ethyl-N-nitrosourea. The oral cavity carcinogen, 4-nitroquinoline-1-oxide (4-NQO; 10 ppm in drinking water; 28 days), was qualified as a positive control for mutagenesis in oral tissues since it caused significant increases in cII MFs in gingiva/palate (50.2-fold) and gingiva/buccal tissues (21.3-fold), but not in liver or bone marrow (0.9- and 1.4-fold, respectively). These results are consistent with the observation that 4-NQO primarily induces tumors in oral cavity. Results also demonstrate the utility of the BB rat mutation assay and optimized methods for investigation of oral cavity mutagenicity, and by extension, analysis of other small and cartilaginous tissues. PMID:25969955

  14. Evaluation of the Effect of Two Different Systemic Doses of Viola Odorata on Prevention of Induced Tongue Dysplasia in Rats

    Directory of Open Access Journals (Sweden)

    Sanaz Helli

    2016-09-01

    Full Text Available Statement of the Problem: Oral cancer is among the ten most common cancers worldwide. It affects the life quality of patients in many ways. Purpose: The aim of this study was to compare the effects of two different systemic doses of Viola Odorata syrup on the prevention of 4-Nitroquinoline-1-oxide (4-NQO induced tongue dysplasia in rats. Materials and Method: Forty-eight male Wistar rats were divided into four groups of A, B, C and D. Group A served as the control group. The rats in groups B to D received 30 ppm of 4-NQO in drinking water for 12 weeks. Additionally, the rats in groups B and C received Viola Odorata syrup at doses of 15 and 5 ml/kg, respectively, 3 times a week. Body weights were measured three times a week. At the end, the rats were euthanized and the tongue was removed. Histological evaluations for carcinogenesis were carried out under a light microscope. Results: The mean body weight of the rats in groups B, C, and D were lower than that in group A (p< 0.01. After 12 weeks of treatment, microscopically no histological changes of the tongue base epithelia were observed in the control group. The rats in group B did not show severe dysplastic changes; only mild to moderate histological changes including hyperplasia and hyperkeratosis were evident. These incidences were significantly more apparent in groups C with moderate to severe changes (p< 0.05 and group D with severe dysplastic changes (p< 0.01. Almost all rats in group D had hyperplasia and manifested all of the stages of dysplasia. Conclusion: Viola Odorata extract has dose-dependent inhibitory effects on the development of tongue induced dysplasia.

  15. The influence of sleep deprivation on expression of apoptosis regulatory proteins p53, bcl-2 and bax following rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide

    Directory of Open Access Journals (Sweden)

    Juliana Noguti

    2013-01-01

    Full Text Available Background: The aim of this study was to evaluate whether paradoxical sleep deprivation could affects the mechanisms and pathways essentials for cancer cells in tongue cancer induced by 4-nitroquinole 1-oxide in Wistar rats. Materials and Methods: For this purpose, the animals were distributed into 4 groups of 5 animals each treated with 50 ppm 4 nitroquinoline 1 oxide (4 NQO solution through their drinking water for 4 and 12 weeks. The animals were submitted to paradoxical sleep deprivation (PSD for 72 h using the modified multiple platform method, which consisted of placing 5 mice in a cage (41 × 34 × 16 cm containing 10 circular platforms (3.5 cm in diameter with water 1 cm below the upper surface. The investigations were conducted using immunohistochemistry of p53, Bax and Bcl-2 proteins related to apoptosis and its pathways. Statistical analysis was performed by Kruskal-Wallis non-parametric test followed by the Dunn′s test using SPSS software pack (version 1.0. P value < 0.05 was considered for statistic significance. Results: Although no histopathological abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure in all groups, in 12 weeks were observed pre-neoplasic lesions. Data analysis revealed statistically significant differences ( P < 0.05 in 4 weeks group for p53 and for bcl-2 and for all immunomarkers after 12 weeks of 4NQO administration. Conclusion: Our results reveal that sleep deprivation exerted alterations in proteins associated with proliferation and apoptosis in carcinogenesis.

  16. Genistein, isoflavonoids in soybeans, prevents the formation of excess radiation-induced centrosomes via p21 up-regulation

    Energy Technology Data Exchange (ETDEWEB)

    Shimada, Mikio; Kato, Akihiro [Department of Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Yoshida-konoe, Sakyo, Kyoto 606-8501 (Japan); Habu, Toshiyuki [Department of Radiation System Biology, Radiation Biology Center, Kyoto University, Kyoto 606-8501 (Japan); Komatsu, Kenshi, E-mail: komatsu@house.rbc.kyoto-u.ac.jp [Department of Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Yoshida-konoe, Sakyo, Kyoto 606-8501 (Japan)

    2011-11-01

    The centrosome is a cytoplasmic organelle which duplicates once during each cell cycle, and the presence of excess centrosomes promote chromosome instability through chromosome missegregation following cytokinesis. Ionizing radiation (IR) can induce extra centrosomes by permitting the continuation of CDK2/Cyclin-A/E-mediated centrosome duplication when cells are arrested in the cell cycle after irradiation. The work described here shows that, in addition to IR, extra centrosomes were induced in human U2OS and mouse NIH3T3 cells after treatment with agents which include DNA adduct-forming chemicals: benzopyrene (BP), 4-nitroquinoline 1-oxide (4NQO), a DNA cross linker: cis-diamminedichloro-platinum (cisplatin), topoisomerase inhibitors: camptothecin, etoposide, genistein, and ultra-violet light (UV). These agents were divided into two categories with respect to the regulation of p21, which is an inhibitor of CDK2/Cyclin-A/E: specifically, p21 was up-regulated by an IR exposure and treatment with topoisomerase inhibitors. However, UV, BP, 4NQO and cisplatin down-regulated p21 below basal levels. When cells were irradiated with IR in combination with all of these agents, except genistein, enhanced induction of extra centrosomes was observed, regardless of the nature of p21 expression. Genistein significantly suppressed the frequency of IR-induced extra centrosomes in a dose-dependent manner, and 20 {mu}g/ml of genistein reduced this frequency to 66%. Consistent with this, genistein substantially up-regulated p21 expression over the induction caused by IR alone, while other agents down-regulated or marginally affected this. This suggests the inhibitory effect of genistein on the induction of extra centrosomes occurs through the inactivation of CDK2/Cyclin-A/E via p21 up-regulation. This hypothesis is supported by the observation that p21 knockdown with siRNA reduced the activity of CDK2/Cyclin-A/E and restored the enhanced effect of a combined treatment with genistein

  17. Isolation and analysis of UV and radio-resistant bacteria from Chernobyl.

    Science.gov (United States)

    Zavilgelsky, G B; Abilev, S K; Sukhodolets, V V; Ahmad, S I

    1998-05-15

    The accident at the Chernobyl nuclear power station in 1986 led to the dispersal of large amounts of a variety of radioactive materials, most importantly uranium, plutonium, 137Cs, 131I and 90Sr, over very large distances estimated to reach as far as Sweden, Norway, Turkey and possibly the USA. As a consequence, the soil on which the radioactive materials fell was contaminated and the degree of contamination varied with distance from the station, the direction and strength of the wind and the amount of atmospheric scavenging by rainfall at that time. Some of the radioactive materials have left a significant impact on mankind in the form of chromosomal aberrations including trisomy, various forms of cancers and death, whilst others are still in the ground where they will remain for a prolonged period to continue to exert their effects. Likewise, microbes living in the soil and exposed to radioactive materials may have been affected in a number of ways; some perished, and others survived due to the acquisition of advantageous mutation. Six years after the accident, soil samples contaminated with different levels of radioactivity were obtained from five regions within a 30 km radius of the nuclear power plant. From these soil samples spore-forming bacilli were isolated, quantified, identified and tested for resistance to X-rays, UVC and 4-nitroquinoline 1-oxide (4NQO). As a control, spore-forming bacilli were obtained from 'Zeleny mys' (an area 50 km south-east of the power station and emitting basal levels of radioactivity). A mutant of Escherichia coli hyper-resistant to a variety of DNA-damaging agents and its parent strain were also included in the study. Analysis of results reveals that a proportion of isolates of the same species from near the power station and the E. coli mutant SA236 were more resistant to X-rays, UVC and 4NQO compared with isolates from the control site and the E. coli parent strain, KL14, respectively. PMID:9679315

  18. Deletion of inositol hexakisphosphate kinase 1 (IP6K1) reduces cell migration and invasion, conferring protection from aerodigestive tract carcinoma in mice.

    Science.gov (United States)

    Jadav, Rathan S; Kumar, Dharmika; Buwa, Natasha; Ganguli, Shubhra; Thampatty, Sitalakshmi R; Balasubramanian, Nagaraj; Bhandari, Rashna

    2016-08-01

    Inositol hexakisphosphate kinases (IP6Ks), a family of enzymes found in all eukaryotes, are responsible for the synthesis of 5-diphosphoinositol pentakisphosphate (5-IP7) from inositol hexakisphosphate (IP6). Three isoforms of IP6Ks are found in mammals, and gene deletions of each isoform lead to diverse, non-overlapping phenotypes in mice. Previous studies show a facilitatory role for IP6K2 in cell migration and invasion, properties that are essential for the early stages of tumorigenesis. However, IP6K2 also has an essential role in cancer cell apoptosis, and mice lacking this protein are more susceptible to the development of aerodigestive tract carcinoma upon treatment with the oral carcinogen 4-nitroquinoline-1-oxide (4NQO). Not much is known about the functions of the equally abundant and ubiquitously expressed IP6K1 isoform in cell migration, invasion and cancer progression. We conducted a gene expression analysis on mouse embryonic fibroblasts (MEFs) lacking IP6K1, revealing a role for this protein in cell receptor-extracellular matrix interactions that regulate actin cytoskeleton dynamics. Consequently, cells lacking IP6K1 manifest defects in adhesion-dependent signaling, evident by lower FAK and Paxillin activation, leading to reduced cell spreading and migration. Expression of active, but not inactive IP6K1 reverses migration defects in IP6K1 knockout MEFs, suggesting that 5-IP7 synthesis by IP6K1 promotes cell locomotion. Actin cytoskeleton remodeling and cell migration support the ability of cancer cells to achieve their complete oncogenic potential. Cancer cells with lower IP6K1 levels display reduced migration, invasion, and anchorage-independent growth. When fed an oral carcinogen, mice lacking IP6K1 show reduced progression from epithelial dysplasia to invasive carcinoma. Thus, our data reveal that like IP6K2, IP6K1 is also involved in early cytoskeleton remodeling events during cancer progression. However, unlike IP6K2, IP6K1 is essential for 4NQO

  19. Deletion of inositol hexakisphosphate kinase 1 (IP6K1) reduces cell migration and invasion, conferring protection from aerodigestive tract carcinoma in mice.

    Science.gov (United States)

    Jadav, Rathan S; Kumar, Dharmika; Buwa, Natasha; Ganguli, Shubhra; Thampatty, Sitalakshmi R; Balasubramanian, Nagaraj; Bhandari, Rashna

    2016-08-01

    Inositol hexakisphosphate kinases (IP6Ks), a family of enzymes found in all eukaryotes, are responsible for the synthesis of 5-diphosphoinositol pentakisphosphate (5-IP7) from inositol hexakisphosphate (IP6). Three isoforms of IP6Ks are found in mammals, and gene deletions of each isoform lead to diverse, non-overlapping phenotypes in mice. Previous studies show a facilitatory role for IP6K2 in cell migration and invasion, properties that are essential for the early stages of tumorigenesis. However, IP6K2 also has an essential role in cancer cell apoptosis, and mice lacking this protein are more susceptible to the development of aerodigestive tract carcinoma upon treatment with the oral carcinogen 4-nitroquinoline-1-oxide (4NQO). Not much is known about the functions of the equally abundant and ubiquitously expressed IP6K1 isoform in cell migration, invasion and cancer progression. We conducted a gene expression analysis on mouse embryonic fibroblasts (MEFs) lacking IP6K1, revealing a role for this protein in cell receptor-extracellular matrix interactions that regulate actin cytoskeleton dynamics. Consequently, cells lacking IP6K1 manifest defects in adhesion-dependent signaling, evident by lower FAK and Paxillin activation, leading to reduced cell spreading and migration. Expression of active, but not inactive IP6K1 reverses migration defects in IP6K1 knockout MEFs, suggesting that 5-IP7 synthesis by IP6K1 promotes cell locomotion. Actin cytoskeleton remodeling and cell migration support the ability of cancer cells to achieve their complete oncogenic potential. Cancer cells with lower IP6K1 levels display reduced migration, invasion, and anchorage-independent growth. When fed an oral carcinogen, mice lacking IP6K1 show reduced progression from epithelial dysplasia to invasive carcinoma. Thus, our data reveal that like IP6K2, IP6K1 is also involved in early cytoskeleton remodeling events during cancer progression. However, unlike IP6K2, IP6K1 is essential for 4NQO

  20. Advances in rodent models of human esophageal squamous cell carcinoma%食管鳞癌动物模型的研究进展

    Institute of Scientific and Technical Information of China (English)

    黄裔腾; 殷秀凯; 钟雪云; 张灏

    2011-01-01

    建立和应用真实模拟人类疾病的动物模型,从整体水平动态地揭示肿瘤发生机制,从而寻找防治对策和开发治疗新药,是成功开展转化医学研究的关键.食管癌是最高发的恶性肿瘤之一.由于相关活体动物模型研究和开发的相对滞后,对于食管鳞癌的病因、发病机制和相关分子通路缺乏全面系统深入的认识,直接导致无法有针对性地进行早期分子诊断标志物和有效药物靶点的开发和转化,严重影响早期诊断和治疗预后.合适的动物模型是改变这一现状的关键.本文就食管鳞癌动物模型的种类、构建和应用方面作一综述,并着重介绍了4-硝基喹啉-氧化物(4NQO)化学致癌结合基因工程的小鼠模型.%Esophageal squamous cell carcinoma (ESCC) is a common form of malignant disease. Appropriate animal models recapitulating human cancers, which are powerful not only for the elucidation of in vivo process and relevantmechanisms of the diseases but also for the evaluation of efficacy and safety of new drugs and management concepts, are critical for the success of translational research. In this context, compared with other malignancies, the present situation for human ESCC that novel discoveries for either diagnostic markers or therapeutic targets as well as the clinical application are out of step (laggard) is largely attributed to the lack of suitable in vivo animal model for this human disease. This article provides an overview of the currently available animal models established for human ESCC, encompassing chemically induced and genetically engineered rodents. Genetically engineered mice coupling induction with 4-nitroquinoline-l-oxide (4NQO) are discussed in more detail.

  1. Formation potentials of typical disinfection byproducts and changes of genotoxicity for chlorinated tertiary effluent pretreated by ozone.

    Science.gov (United States)

    Cao, Nan; Miao, Tingting; Li, Kuixiao; Zhang, Yu; Yang, Min

    2009-01-01

    The effects of ozonation on the formation potential of typical disinfection byproducts (DBPs) and the changes of genotoxicity during post chlorination of tertiary effluent from a sewage treatment plant were investigated. Ozonation enhanced the yields of all detected chlorine DBPs except CHCl3. At a chlorine dose of 5 mg/L, the three brominated THMs and five HAAs increased, while chloroform decreased with the increase of ozone dose from 0 to 10 mg/L (ozone dose in consumption base). At a chlorine dose of 10 mg/L, the two mixed bromochloro species THMs and two dominant HAAs (DCAA and TCAA) increased firstly and then decreased with the increase of ozone dose, with the turning point approximately occurring at an ozone dose of 5 mg/L. The genotoxicity detected using umu test, on the other hand, was removed from 7 microg 4-NQO/L to a negligible level by ozonation under an ozone dose of 5 mg/L. Chlorination could further remove the genotoxicity to some extent. It was found that SUVA (UV absorbance divided by DOC concentration) might be used as an indicative parameter for monitoring the removal of genotoxicity during the oxidation.

  2. The Inhibitory Effects of Aqueous Extract from Guava Twigs, Psidium guajava L., on Mutation and Oxidative Damage

    Directory of Open Access Journals (Sweden)

    Zhi-Chyang Kang

    2013-01-01

    Full Text Available This study examines the inhibitory effects of the aqueous extract from guava twigs (GTE, Psidium guajava L., on mutation and oxidative damage. The results show that GTE inhibits the mutagenicity of 4-nitroquinoline-N-oxide (4-NQO, a direct mutagen, and 2-aminoanthracene (2-AA, an indirect mutagen, toward Salmonella typhimurium TA 98 and TA 100. In addition, GTE shows radical scavenging, reducing activities, tyrosinase inhibition, and liposome protection effects. Meanwhile, GTE in the range of 0.1–0.4 mg/mL protects liver cells from tert-butyl-hydroperoxide-(t-BHP- induced cytotoxicity. Furthermore, the cytotoxicity inhibition of GTE in the t-BHP-treated cells was demonstrated in a dose-dependent manner. High-performance liquid chromatography analysis suggests that the major phenolic constituents in GTE are gallic acid, ferulic acid, and myricetin. These active phenolic components may contribute to the biological protective effects of GTE in different models. The data suggest that GTE exhibiting biological activities can be applied to antimutation, antityrosinase, and antioxidative damage.

  3. Inhibitory effect of aqueous extracts from Miracle Fruit leaves on mutation and oxidative damage.

    Science.gov (United States)

    Chen, Tai-Yuan; Kang, Zhi-Chyang; Yen, Ming-Tsung; Huang, Ming-Hsing; Wang, Bor-Sen

    2015-02-15

    This study investigated the inhibitory effects of aqueous extracts from Miracle Fruit leaves (AML) on mutation and oxidative damage. The results showed that AML in the range of 1-5mg/plate inhibited the mutagenicity of 2-aminoanthracene (2-AA), an indirect mutagen, and 4-nitroquinoline-N-oxide (4-NQO), a direct mutagen toward Salmonella typhimurium TA 98 and TA 100. On the other hand, AML in the range of 0.05-0.2mg/ml showed radical scavenging, reducing activities, liposome protection as well as decreased tert-butyl hydroperoxide (t-BHP) induced oxidative cytotoxicity in HepG2 cells. High performance liquid chromatography (HPLC) analysis suggested that the active phenolic constituents in AML are p-hydroxybenzoic acid, vanillic acid, syringic acid, trans-p-coumaric acid and veratric acid. These active phenolic components may contribute to the biological protection effects of AML in different models. The data suggest that AML exhibiting biological activities can be applied to antimutation as well as anti-oxidative damage. PMID:25236245

  4. A Synthetic Interaction between CDC20 and RAD4 in Saccharomyces cerevisiae upon UV Irradiation

    Directory of Open Access Journals (Sweden)

    Bernadette Connors

    2014-01-01

    Full Text Available Regulation of DNA repair can be achieved through ubiquitin-mediated degradation of transiently induced proteins. In Saccharomyces cerevisiae, Rad4 is involved in damage recognition during nucleotide excision repair (NER and, in conjunction with Rad23, recruits other proteins to the site of damage. We identified a synthetic interaction upon UV exposure between Rad4 and Cdc20, a protein that modulates the activity of the anaphase promoting complex (APC/C, a multisubunit E3 ubiquitin ligase complex. The moderately UV sensitive Δrad4 strain became highly sensitive when cdc20-1 was present, and was rescued by overexpression of CDC20. The double mutant is also deficient in elicting RNR3-lacZ transcription upon exposure to UV irradiation or 4-NQO compared with the Δrad4 single mutant. We demonstrate that the Δrad4/cdc20-1 double mutant is defective in double strand break repair by way of a plasmid end-joining assay, indicating that Rad4 acts to ensure that damaged DNA is repaired via a Cdc20-mediated mechanism. This study is the first to present evidence that Cdc20 may play a role in the degradation of proteins involved in nucleotide excision repair.

  5. Novel pattern of post-γ ray de novo DNA synthesis in a radioresistant human strain

    International Nuclear Information System (INIS)

    Enhanced resistance to radiation cytotoxicity in a fibroblast strain from an afflicted member of a Li-Fraumeni syndrome family may be largely ascribable to a change in the pattern of DNA replicative synthesis following γ ray exposure. That is, the extent of the initial radiogenic inhibition of replicative synthesis and the time interval before its subsequent recovery were both found to be greater in radioresistant (RR) compared to normal cells. In addition, the post-recovery replication rates in the RR cells were both higher and longer lasting than those in the control cells. A similar differential pattern was also seen following treatment with 4NQO, another DNA-damaging agent to which this RR strain displays enhanced resistance. Moreover, several conventional DNA repair assays indicated that the RR cells repair radiogenic damage at normal rates. The authors therefore suggest that the increased inhibition and prolonged lag in resumption of replicative synthesis seen in the RR strain upon exposure to certain genotoxic agents may enhance cellular recovery by ''buying additional time'' for processing of potentially lethal lesions

  6. Identification of new RECQL4 mutations in Caucasian Rothmund-Thomson patients and analysis of sensitivity to a wide range of genotoxic agents

    Energy Technology Data Exchange (ETDEWEB)

    Caseira Cabral, Rosa Estela [Laboratoire ' Genomes et Cancers' , FRE2939 CNRS, Institut Gustave-Roussy, Universite Paris-Sud, PRII, 39 Rue Camille Desmoulins, 94805 Villejuif (France); Instituto de Biofisica Carlos Chagas Filho, Centro de Ciencias da Saude, Universidade Federal do Rio de Janeiro (Brazil); Queille, Sophie [Laboratoire ' Genomes et Cancers' , FRE2939 CNRS, Institut Gustave-Roussy, Universite Paris-Sud, PRII, 39 Rue Camille Desmoulins, 94805 Villejuif (France); Bodemer, Christine; Prost, Yves de [Service de Dermatologie, Hopital Necker-Enfants Malades, Universite Decartes-Paris V, APHP, Cedex (France); Bispo Cabral Neto, Januario [Instituto de Biofisica Carlos Chagas Filho, Centro de Ciencias da Saude, Universidade Federal do Rio de Janeiro (Brazil); Sarasin, Alain [Laboratoire ' Genomes et Cancers' , FRE2939 CNRS, Institut Gustave-Roussy, Universite Paris-Sud, PRII, 39 Rue Camille Desmoulins, 94805 Villejuif (France); Daya-Grosjean, Leela [Laboratoire ' Genomes et Cancers' , FRE2939 CNRS, Institut Gustave-Roussy, Universite Paris-Sud, PRII, 39 Rue Camille Desmoulins, 94805 Villejuif (France)], E-mail: daya@igr.fr

    2008-08-25

    Rothmund-Thomson syndrome (RTS), a rare recessive autosomal disorder, presents genome instability and clinical heterogeneity with growth deficiency, skin and bone defects, premature aging symptoms and cancer susceptibility. A subset of RTS patients presents mutations of the RECQL4 gene, member of the RecQ family of DNA helicases, including the RECQL2 (BLM) and RECQL3 (WRN) genes, defective in the cancer prone Bloom and Werner syndromes, respectively. Analysis of the RECQL4 gene in six clinically diagnosed RTS patients shows five patients, including two siblings, with eight mutations mainly located in the helicase domain, three patients presenting two mutations. The alterations include four missense mutations, one nonsense mutation and the same frameshift deletion, g.2881delG in exon 9 found in three patients. Seven RECQL4 polymorphisms, two being new, have also been identified. Primary RTS fibroblasts from these RTS patients show no sensitivity to a wide variety of genotoxic agents including ionizing or ultraviolet irradiation, nitrogen mustard, 4NQO, 8-MOP, Cis-Pt, MMC, H{sub 2}O{sub 2}, HU, or UV plus caffeine which could be related to the RECQL4 alterations identified here. This is in contrast with the DNA damage sensitive Bloom and Werner cells and highlights the complexity of the numerous RecQ protein functions implicated in the different cellular pathways required for maintaining genomic integrity.

  7. Changes in the components and biotoxicity of dissolved organic matter in a municipal wastewater reclamation reverse osmosis system.

    Science.gov (United States)

    Sun, Ying-Xue; Hu, Hong-Ying; Shi, Chun-Zhen; Yang, Zhe; Tang, Fang

    2016-09-01

    The characteristics of dissolved organic matter (DOM) and the biotoxicity of these components were investigated in a municipal wastewater reclamation reverse osmosis (mWRRO) system with a microfiltration (MF) pretreatment unit. The MF pretreatment step had little effect on the levels of dissolved organic carbon (DOC) in the secondary effluent, but the addition of chlorine before MF promoted the formation of organics with anti-estrogenic activity. The distribution of excitation emission matrix (EEM) fluorescence constituents exhibited obvious discrepancies between the secondary effluent and the reverse osmosis (RO) concentrate. Using size exclusion chromatography, DOM with low molecular weights of approximately 1.2 and 0.98 kDa was newly formed during the mWRRO. The normalized genotoxicity and anti-estrogenic activity of the RO concentrate were 32.1 ± 10.2 μg4-NQO/mgDOC and 0.36 ± 0.08 mgTAM/mgDOC, respectively, and these values were clearly higher than those of the secondary effluent and MF permeate. The florescence volume of Regions I and II in the EEM spectrum could be suggested as a surrogate for assessing the genotoxicity and anti-estrogenic activity of the RO concentrate.

  8. Identification of novel human damage response proteins targeted through yeast orthology.

    Directory of Open Access Journals (Sweden)

    J Peter Svensson

    Full Text Available Studies in Saccharomyces cerevisiae show that many proteins influence cellular survival upon exposure to DNA damaging agents. We hypothesized that human orthologs of these S. cerevisiae proteins would also be required for cellular survival after treatment with DNA damaging agents. For this purpose, human homologs of S. cerevisiae proteins were identified and mapped onto the human protein-protein interaction network. The resulting human network was highly modular and a series of selection rules were implemented to identify 45 candidates for human toxicity-modulating proteins. The corresponding transcripts were targeted by RNA interference in human cells. The cell lines with depleted target expression were challenged with three DNA damaging agents: the alkylating agents MMS and 4-NQO, and the oxidizing agent t-BuOOH. A comparison of the survival revealed that the majority (74% of proteins conferred either sensitivity or resistance. The identified human toxicity-modulating proteins represent a variety of biological functions: autophagy, chromatin modifications, RNA and protein metabolism, and telomere maintenance. Further studies revealed that MMS-induced autophagy increase the survival of cells treated with DNA damaging agents. In summary, we show that damage recovery proteins in humans can be identified through homology to S. cerevisiae and that many of the same pathways are represented among the toxicity modulators.

  9. Construction of a nrdA::luxCDABE Fusion and Its Use in Escherichia coli as a DNA Damage Biosensor

    Directory of Open Access Journals (Sweden)

    Man Bock Gu

    2008-02-01

    Full Text Available The promoter of nrdA gene which is related with DNA synthesis was used to construct a DNA damage sensitive biosensor. A recombinant bioluminescent E. coli strain, BBTNrdA, harboring a plasmid with the nrdA promoter fused to the luxCDABE operon, was successfully constructed. Its response to various chemicals including genotoxic chemicals substantiates it as a DNA damage biosensor. In characterization, three different classes of toxicants were used: DNA damaging chemicals, oxidative stress chemicals, and phenolics. BBTNrdA only responded strongly to DNA damaging chemicals, such as nalidixic acid (NDA, mitomycin C (MMC, 1-methyl-1-nitroso-N-methylguanidine (MNNG, and 4-nitroquinoline N-oxide (4-NQO. In contrast, there were no responses from the oxidative stress chemicals and phenolics, except from hydrogen peroxide (H2O2 which is known to cause DNA damage indirectly. Therefore, the results of the study demonstrate that BBTNrdA can be used as a DNA damage biosensor.

  10. Formation potentials of typical DBPs and changes of genotoxicity for chlorinated tertiary effluent pretreated by ozone

    Institute of Scientific and Technical Information of China (English)

    CAO Nan; MIAO Tingting; LI Kuixiao; ZHANG Yu; YANG Min

    2009-01-01

    The effects of ozonation on the formation potential of typical disinfection byproducts (DBPs) and the changes of genotoxicity during post chlorination of tertiary effluent from a sewage treatment plant were investigated. Ozonation enhanced the yields of all detected chlorine DBPs except CHCl3. At a chlorine dose of 5 mg/L, the three brominated THMs and five HAAs increased, while chloroform decreased with the increase of ozone dose from 0 to 10 mg/L (ozone dose in consumption base). At a chlorine dose of 10 mg/L, the two mixed bromochloro species THMs and two dominant HAAs (DCAA and TCAA) firstly increased and then decreased with the increase of ozone dose, with the turning point approximately occurring at an ozone dose of 5 mg/L. The genotoxicity detected using umu test, on the other hand, was removed from 7 μg 4-NQO/L to a negligible level by ozonation under an ozone dose of 5 mg/L. Chlorination could further remove the genotoxicity to some extent. It was found that SUVA (UV absorbance divided by DOC concentration) might be used as an indicative parameter for monitoring the removal of genotoxicity during the oxidation.

  11. Early induction of cytokines/cytokine receptors and Cox2, and activation of NF-κB in 4-nitroquinoline 1-oxide-induced murine oral cancer model

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yu-Ching [Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan (China); Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan (China); Ho, Heng-Chien; Lee, Miau-Rong [Department of Biochemistry, China Medical University, Taichung 404, Taiwan (China); Lai, Kuang-Chi [Department of Surgery, China Medical University Beigang Hospital, Yunlin 651, Taiwan (China); School of Medicine, China Medical University, Taichung 404, Taiwan (China); Yeh, Chung-Min; Lin, Yueh-Min [Department of Pathology, Changhua Christian Hospital, Changhua 500, Taiwan (China); Ho, Tin-Yun [School of Chinese Medicine, China Medical University, Taichung 404, Taiwan (China); Hsiang, Chien-Yun, E-mail: cyhsiang@mail.cmu.edu.tw [Department of Microbiology, China Medical University, Taichung 404, Taiwan (China); Chung, Jing-Gung, E-mail: jgchung@mail.cmu.edu.tw [Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan (China); Department of Biotechnology, Asia University, Taichung 413, Taiwan (China)

    2012-07-15

    The purpose of this study was to identify the genes induced early in murine oral carcinogenesis. Murine tongue tumors induced by the carcinogen, 4-nitroquinoline 1-oxide (4-NQO), and paired non-tumor tissues were subjected to microarray analysis. Hierarchical clustering of upregulated genes in the tumor tissues revealed an association of induced genes with inflammation. Cytokines/cytokine receptors induced early were subsequently identified, clearly indicating their involvement in oral carcinogenesis. Hierarchical clustering also showed that cytokine-mediated inflammation was possibly linked with Mapk6. Cox2 exhibited the greatest extent (9–18 fold) of induction in the microarray data, and its early induction was observed in a 2 h painting experiment by RT-PCR. MetaCore analysis showed that overexpressed Cox2 may interact with p53 and transcriptionally inhibit expression of several downstream genes. A painting experiment in transgenic mice also demonstrated that NF-κB activates early independently of Cox2 induction. MetaCore analysis revealed the most striking metabolic alterations in tumor tissues, especially in lipid metabolism resulting from the reduction of Pparα and Rxrg. Reduced expression of Mapk12 was noted, and MetaCore analysis established its relationship with decreased efficiency of Pparα phosphorylation. In conclusion, in addition to cytokines/cytokine receptors, the early induction of Cox2 and NF-κB activation is involved in murine oral carcinogenesis.

  12. Therapeutic Efficacy of Orally Delivered Doxorubicin Nanoparticles in Rat Tongue Cancer Induced by 4-Nitroquinoline 1-Oxide

    Directory of Open Access Journals (Sweden)

    Monir Moradzadeh Khiavi

    2015-06-01

    Full Text Available Purpose: Oral cancer is one of the most significant cancers in the world, and squamous cell carcinoma makes up about 94% of oral malignancies. The aim of the present study was to compare the efficacy of doxorubicin plus methotrexate - loaded nanoparticles on tongue squamous cell carcinoma induced by 4NQO and compare it with the commercial doxorubicin and methotrexate delivered orally on seventy SD male rats. Methods: 70 rats were divided into five groups. During the study, the animals were weighed by a digital scale once a week. Number of mortalities was recorded in the data collection forms. At the end of the treatment, biopsy samples were taken from rat tongues in order to evaluate the severity of dysplasia and the extent of cell proliferation. The results were analyzed using ANOVA, descriptive statistics and chi-square test. Results: No statistically significant difference was found in the mean weight of five groups (p>0.05. No significant relationship was found between groups and mortality rate (P = 0. 39. In addition, there was a significant relationship between groups and the degree of dysplasia (P <0.001. The statistical analysis showed a significant relationship between groups and the rate of cell proliferation (p <0.001. Conclusion: The results of the present study showed that the use of doxorubicin plus methotrexate - loaded nanoparticles orally had more therapeutic effects than commercial doxorubicin plus methotrexate.

  13. The histone demethylase LSD1 is a novel oncogene and therapeutic target in oral cancer.

    Science.gov (United States)

    Wang, Yanling; Zhu, Yumin; Wang, Qiong; Hu, Huijun; Li, Zhongwu; Wang, Dongmiao; Zhang, Wei; Qi, Bin; Ye, Jinhai; Wu, Heming; Jiang, Hongbing; Liu, Laikui; Yang, Jianrong; Cheng, Jie

    2016-04-28

    The histone demethylase LSD1 functions as a key pro-oncogene and attractive therapeutic target in human cancer. Here we sought to interrogate the oncogenic roles of LSD1 in OSCC tumorigenesis and therapeutic intervention by integrating chemical-induced OSCC model, genetic and pharmacological loss-of-function approaches. Our data revealed that aberrant LSD1 overexpression in OSCC was significantly associated with tumor aggressiveness and shorter overall survival. Increased abundance of LSD1 was detected along with disease progression in DMBA- or 4NQO-induced OSCC animal models. LSD1 depletion via siRNA-mediated knockdown in OSCC cells resulted in impaired cell proliferation, migration/invasion, tumorsphere formation and reduced xenograft growth while inducing cell apoptosis and enhancing chemosensitivity to 5-FU. Moreover, treatments of LSD1 chemical inhibitors (pargyline and tranylcypromine) induced its protein reduction probably via enhanced protein degradation and produced similar phenotypic changes resembling LSD1 silencing in OSCC cells. Pharmacological inhibition of LSD1 by intraperitoneal delivery of these inhibitors resulted in impaired xenograft overgrowth. Taken together, our data reveal the tumorigenic roles of LSD1 and identified LSD1 as a novel biomarker with diagnostic and prognostic significance, and also establish that targeting LSD1 by chemical inhibitors is a viable therapeutic strategy against OSCC. PMID:26872725

  14. Early induction of cytokines/cytokine receptors and Cox2, and activation of NF-κB in 4-nitroquinoline 1-oxide-induced murine oral cancer model

    International Nuclear Information System (INIS)

    The purpose of this study was to identify the genes induced early in murine oral carcinogenesis. Murine tongue tumors induced by the carcinogen, 4-nitroquinoline 1-oxide (4-NQO), and paired non-tumor tissues were subjected to microarray analysis. Hierarchical clustering of upregulated genes in the tumor tissues revealed an association of induced genes with inflammation. Cytokines/cytokine receptors induced early were subsequently identified, clearly indicating their involvement in oral carcinogenesis. Hierarchical clustering also showed that cytokine-mediated inflammation was possibly linked with Mapk6. Cox2 exhibited the greatest extent (9–18 fold) of induction in the microarray data, and its early induction was observed in a 2 h painting experiment by RT-PCR. MetaCore analysis showed that overexpressed Cox2 may interact with p53 and transcriptionally inhibit expression of several downstream genes. A painting experiment in transgenic mice also demonstrated that NF-κB activates early independently of Cox2 induction. MetaCore analysis revealed the most striking metabolic alterations in tumor tissues, especially in lipid metabolism resulting from the reduction of Pparα and Rxrg. Reduced expression of Mapk12 was noted, and MetaCore analysis established its relationship with decreased efficiency of Pparα phosphorylation. In conclusion, in addition to cytokines/cytokine receptors, the early induction of Cox2 and NF-κB activation is involved in murine oral carcinogenesis.

  15. CDH1基因在SD大鼠舌黏膜癌变过程中甲基化和突变的研究%Study on the Methylation and Mutation of CDH1 in the Process of SD Rats Tongue Carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    王君莲; 张绪; 毛亮; 谭红; 廖鹏程; 聂敏海

    2016-01-01

    目的:通过甲基化和外显子突变研究探索CDH1基因在舌鳞状细胞癌发生过程中的作用.方法:采用质量分数为0.004%的4-硝基喹啉-1-氧化物(4-nitroquinoline-1-oxide,4NQO)饮水饲养90只无特定病原体(specific pathogen free,SPF)SD大鼠以诱发舌黏膜癌变全过程,分别于第10、14、18、22、24周分批处死大鼠,取舌黏膜组织行病理分级,并提取基因组DNA.利用甲基化特异性PCR(methylation-specific PCR,MS-PCR)检测CDH1启动子甲基化水平;利用聚合酶链式反应(polymerase chain reaction,PCR)扩增CDH1外显子1-16,提纯后测序以检测突变.结果:病变各阶段均未检测出CDH1启动子甲基化产物,CDH1 mRNA第2106位发生碱基G→T错义突变.结论:4NQO饮水诱导SD大鼠舌黏膜癌变的发生、发展可能与CDH1外显子突变有关而与CDH1启动子甲基化无关.

  16. 5MeCDDO Blocks Metabolic Activation but not Progression of Breast, Intestine, and Tongue Cancers. Is Antioxidant Response Element a Prevention Target?

    Science.gov (United States)

    Lubet, Ronald A; Townsend, Reid; Clapper, Margie L; Juliana, M Margaret; Steele, Vernon E; McCormick, David L; Grubbs, Clinton J

    2016-07-01

    The preventive efficacy of the triterpenoid 5MeCDDO was tested in two models of mammary cancer, the Min model of intestinal cancer, and a chemically induced model of head and neck cancer. In one model of mammary cancer, female Sprague-Dawley rats were administered MNU at 50 days of age, and 5MeCDDO (27 ppm) was administered in the diet beginning 5 days later for the duration of the study; 5MeCDDO was ineffective. In contrast, in a model examining initiation of mammary cancers by the procarcinogen dimethyl-benzanthracene, 5, 6-benzoflavone (500 ppm, an Ah receptor agonist) or 5MeCDDO (27 or 2.7 ppm) decreased tumor multiplicity by 90%, 80%, and 50%, respectively. This anti-initiating effect which is presumably mediated by altered metabolic activation parallels our observation that 5MeCDDO induced proteins of various antioxidant response element (ARE)-related phase II drug-metabolizing enzymes [e.g., GST Pi, AKR 7A3 (aflatoxicol), epoxide hydrolase, and quinone reductase] in the liver. 5MeCDDO tested in the 4-nitroquinoline-l-oxide (4-NQO) head and neck cancer model failed to decrease tumor incidence or invasiveness. In the Min mouse model of intestinal cancer, a high dose of 5MeCDDO (80 ppm) was weakly effective in reducing adenoma multiplicity [∼30% (P < 0.05)]; however, a lower dose was totally ineffective. These findings question whether measuring increased levels of certain ARE-related genes (e.g., quinone reductase, GST Pi), indicating decreased carcinogen activation are sufficient to imply general chemopreventive efficacy of a given agent or mixture. Cancer Prev Res; 9(7); 616-23. ©2016 AACR. PMID:27150634

  17. Induction and repair of DNA damage measured by the comet assay in human T lymphocytes separated by immunomagnetic cell sorting.

    Science.gov (United States)

    Bausinger, Julia; Speit, Günter

    2014-11-01

    The comet assay is widely used in human biomonitoring to measure DNA damage in whole blood or isolated peripheral blood mononuclear cells (PBMC) as a marker of exposure to genotoxic agents. Cytogenetic assays with phytohemagglutinin (PHA)-stimulated cultured T lymphocytes are also frequently performed in human biomonitoring. Cytogenetic effects (micronuclei, chromosome aberrations, sister chromatid exchanges) may be induced in vivo but also occur ex vivo during the cultivation of lymphocytes as a consequence of DNA damage present in lymphocytes at the time of sampling. To better understand whether DNA damage measured by the comet assay in PBMC is representative for DNA damage in T cells, we comparatively investigated DNA damage and its repair in PBMC and T cells obtained by immunomagnetic cell sorting. PBMC cultures and T cell cultures were exposed to mutagens with different modes of genotoxic action and DNA damage was measured by the comet assay after the end of a 2h exposure and after 18h post-incubation. The mutagens tested were methyl methanesulfonate (MMS), (±)-anti-B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE), 4-nitroquinoline-1-oxide (4NQO), styrene oxide and potassium bromate. MMS and potassium bromate were also tested by the modified comet assay with formamido pyrimidine glycosylase (FPG) protein. The results indicate that the mutagens tested induce DNA damage in PBMC and T cells in the same range of concentrations and removal of induced DNA lesions occurs to a comparable extent. Based on these results, we conclude that the comet assay with PBMC is suited to predict DNA damage and its removal in T cells.

  18. The upr-1 gene encodes a catalytic subunit of the DNA polymerase zeta which is involved in damage-induced mutagenesis in Neurospora crassa.

    Science.gov (United States)

    Sakai, W; Ishii, C; Inoue, H

    2002-05-01

    The upr-1 mutant was one of the first mutagen-sensitive mutants to be isolated in Neurospora crassa. However, the function of the upr-1 gene has not yet been elucidated, although some genetic and biochemical data have been accumulated. In order to clone the upr-1 gene, we performed a chromosome walk from the mat locus, the closest genetic marker to upr-1 for which a molecular probe was available, towards the centromere, and a chromosomal contig of about 300-400 kb was constructed. Some of these clones complemented the temperature sensitivity of the un-16 mutation, which is located between mat and upr-1. The un-16 gene was sequenced, and localized in the MIPS Neurospora crassa genome database. We then searched the regions flanking un-16 for homologs of known DNA repair genes, and found a gene homologous to the REV3 gene of budding yeast. The phenotype of the upr-1 mutant is similar to that of the yeast rev3 mutant. An ncrev3 mutant carrying mutations in the N. crassa REV3 homolog was constructed using the RIP (repeat-induced point mutation) process. The spectrum of mutagen sensitivity of the ncrev3 mutant was similar to that of the upr-1 mutant. Complementation tests between the upr-1 and ncrev3 mutations indicated that the upr-1 gene is in fact identical to the ncrev3 gene. To clarify the role of the upr-1 gene in DNA repair, the frequency of MMS and 4NQO-induced mutations was assayed using the ad-8 reversion test. The upr-1 mutant was about 10 times less sensitive to both chemicals than the wild type. The expression level of the upr-1 gene is increased on exposure to UV irradiation in the uvs-2 and mus-8 mutants, which belong to postreplication repair group, as well as in the wild type. All these results suggest that the product of the upr-1 gene functions in damage-induced mutagenesis and DNA translesion synthesis in N. crassa.

  19. In vivo induction of phase II detoxifying enzymes, glutathione transferase and quinone reductase by citrus triterpenoids

    Directory of Open Access Journals (Sweden)

    Ahmad Hassan

    2010-09-01

    Full Text Available Abstract Background Several cell culture and animal studies demonstrated that citrus bioactive compounds have protective effects against certain types of cancer. Among several classes of citrus bioactive compounds, limonoids were reported to prevent different types of cancer. Furthermore, the structures of citrus limonoids were reported to influence the activity of phase II detoxifying enzymes. The purpose of the study was to evaluate how variations in the structures of citrus limonoids (namely nomilin, deacetyl nomilin, and isoobacunoic acid and a mixture of limonoids would influence phase II enzyme activity in excised tissues from a mouse model. Methods In the current study, defatted sour orange seed powder was extracted with ethyl acetate and subjected to silica gel chromatography. The HPLC, NMR and mass spectra were used to elucidate the purity and structure of compounds. Female A/J mice were treated with three limonoids and a mixture in order to evaluate their effect on phase II enzymes in four different tissues. Assays for glutathione S-transferase and NAD(PH: quinone reductase (QR were used to evaluate induction of phase II enzymatic activity. Results The highest induction of GST against 1-chloro-2,4-dinitrobenzene (CDNB was observed in stomach (whole, 58% by nomilin, followed by 25% isoobacunoic acid and 19% deacetyl nomilin. Deacetyl nomilin in intestine (small as well as liver significantly reduced GST activity against CDNB. Additionally isoobacunoic acid and the limonoid mixture in liver demonstrated a significant reduction of GST activity against CDNB. Nomilin significantly induced GST activity against 4-nitroquinoline 1-oxide (4NQO, intestine (280% and stomach (75% while deacetyl nomilin showed significant induction only in intestine (73%. Induction of GST activity was also observed in intestine (93% and stomach (45% treated with the limonoid mixture. Finally, a significant induction of NAD(PH: quinone reductase (QR activity was

  20. Resting potential, oncogene-induced tumorigenesis, and metastasis: the bioelectric basis of cancer in vivo

    Science.gov (United States)

    Lobikin, Maria; Chernet, Brook; Lobo, Daniel; Levin, Michael

    2012-12-01

    Cancer may result from localized failure of instructive cues that normally orchestrate cell behaviors toward the patterning needs of the organism. Steady-state gradients of transmembrane voltage (Vmem) in non-neural cells are instructive, epigenetic signals that regulate pattern formation during embryogenesis and morphostatic repair. Here, we review molecular data on the role of bioelectric cues in cancer and present new findings in the Xenopus laevis model on how the microenvironment's biophysical properties contribute to cancer in vivo. First, we investigated the melanoma-like phenotype arising from serotonergic signaling by ‘instructor’ cells—a cell population that is able to induce a metastatic phenotype in normal melanocytes. We show that when these instructor cells are depolarized, blood vessel patterning is disrupted in addition to the metastatic phenotype induced in melanocytes. Surprisingly, very few instructor cells need to be depolarized for the hyperpigmentation phenotype to occur; we present a model of antagonistic signaling by serotonin receptors that explains the unusual all-or-none nature of this effect. In addition to the body-wide depolarization-induced metastatic phenotype, we investigated the bioelectrical properties of tumor-like structures induced by canonical oncogenes and cancer-causing compounds. Exposure to carcinogen 4-nitroquinoline 1-oxide (4NQO) induces localized tumors, but has a broad (and variable) effect on the bioelectric properties of the whole body. Tumors induced by oncogenes show aberrantly high sodium content, representing a non-invasive diagnostic modality. Importantly, depolarized transmembrane potential is not only a marker of cancer but is functionally instructive: susceptibility to oncogene-induced tumorigenesis is significantly reduced by forced prior expression of hyperpolarizing ion channels. Importantly, the same effect can be achieved by pharmacological manipulation of endogenous chloride channels, suggesting

  1. Expressão de galectina-3 e beta-catenina em lesões pré-malignas e carcinomatosas de língua de camundongos Galectin-3 and beta-catenin expression in premalignant and carcinomatous lesions in tongue of mice

    Directory of Open Access Journals (Sweden)

    Juliana Moreira de Almeida Sant'ana

    2011-02-01

    Full Text Available INTRODUÇÃO: A galectina-3 (GAL3 apresenta importantes papéis na biologia tumoral e recentemente foi mostrada a sua participação na via de sinalização Wnt, translocando a beta-catenina para o núcleo. Expressão alterada de GAL3 e beta-catenina tem sido descrita em cânceres, mas não há estudos avaliando a expressão de ambas em displasias e carcinomas desenvolvidos em modelos de carcinogênese de língua. OBJETIVOS: Estudar a expressão de GAL3 e beta-catenina em lesões displásicas e carcinomas induzidos experimentalmente em língua de camundongos. MATERIAL E MÉTODOS: Vinte camundongos C57BL/6 machos foram desafiados com 4NQO na água de beber por 16 semanas e sacrificados na semana 16 e 32. Após o sacrifício, as línguas foram removidas, processadas, coradas por hematoxilina e eosina (HE para detecção de displasias e carcinomas. Ensaio imuno-histoquímico foi realizado para determinar o índice de positividade para GAL3 e beta-catenina nessas lesões, bem como uma correlação entre elas em carcinomas. RESULTADOS: O número de camundongos afetados por carcinoma aumentou entre as semanas 16 e 32 (22,2% vs. 88,9% e o de displasia diminuiu (66,7% vs. 11,1%. Um aumento de células positivas para beta-catenina não membranosa e GAL3 citoplasmática foi observado nas displasias e nos carcinomas, mas essa diferença não foi estatisticamente significativa. No entanto, um aumento estatisticamente significativo de GAL3 nuclear foi observado na evolução de displasia para carcinoma (p = 0,04. Nenhuma correlação foi encontrada entre beta-catenina e GAL3. CONCLUSÃO: Tanto nas displasias quanto nos carcinomas a via de sinalização Wnt está ativa, e o aumento de GAL3 nuclear nos carcinomas sugere um papel na transformação maligna do epitélio lingual.INTRODUCTION: Galectin-3 plays pivotal role in tumor biology and its participation in Wnt signaling pathway translocating beta-catenin into the nucleus has been recently demonstrated