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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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    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Enhanced levels of glutathione and protein glutathiolation in rat tongue epithelium during 4-NQO-induced carcinogenesis.

    Science.gov (United States)

    Huang, Zhishan; Komninou, Despina; Kleinman, Wayne; Pinto, John T; Gilhooly, Elaine M; Calcagnotto, Ana; Richie, John P

    2007-04-01

    High glutathione (GSH) levels are commonly found in oral tumors and are thought to play an important role in tumorigenesis. While posttranslational binding of GSH to cellular proteins (protein glutathiolation) has recently been recognized as an important redox-sensitive regulatory mechanism, no data currently exist on this process during carcinogenesis. Our goal was to determine the effects of 4-nitroquinoline-N-oxide (4-NQO)-induced carcinogenesis on tongue levels of protein-bound and free GSH and related thiols in the rat. Male F-344 rats (6 weeks of age) were administered either 4-NQO (20 ppm) in drinking water or tap water alone (controls) for 8 weeks. Twenty-four weeks after cessation of 4-NQO, squamous cell carcinomas of the tongue were observed in all rats. The levels of both free and bound GSH in tumors, as well as in adjacent tissues, were 2- to 3-fold greater than in tongue epithelium from control rats (p tongue tissues from control rats (ptongue tissues from 4-NQO treated vs. control rats (p<0.05). Altogether, these results suggest that protein glutathiolation, together with GSH and GSSG levels, are induced during oral carcinogenesis in the rat possibly as a result of enhanced levels of oxidative stress.

  6. Inhibition of 4NQO-Induced Oral Carcinogenesis by Dietary Oyster Shell Calcium.

    Science.gov (United States)

    Chen, Ying; Jiang, Yi; Liao, Liyan; Zhu, Xiaoxin; Tang, Shengan; Yang, Qing; Sun, Lihua; Li, Yujie; Gao, Shuangrong; Xie, Zhongjian

    2016-03-01

    Oyster has gained much attention recently for its anticancer activity but it is unclear whether calcium, the major antitumor ingredient in oyster shell, is responsible for the anticarcinogenic role of the oyster. To address this issue, C57BL/6 mice were fed with the carcinogen 4-nitroquinoline-1-oxide (4NQO, 50 µg/mL) and normal diet or a diet containing oyster powder, oyster calcium, or calcium depleted oyster powder. The tongue tissue specimens isolated from these mice were histologically evaluated for hyperplasia, dysplasia, and papillary lesions, and then analyzed for proliferation and differentiation markers by immunohistochemistry. The results showed that mice on the diet containing oyster calcium significantly reduced rates of tumors in the tongue and proliferation and enhanced differentiation in the oral epithelium compared with the diet containing calcium depleted oyster powder. These results suggest that calcium in oyster plays a critical role in suppressing formation of oral squamous cell carcinoma and proliferation and promoting differentiation of the oral epithelium.

  7. Expression of KLF5 in 4NQO-induced mouse tongue carcinogenesis%Krüppel样因子5在小鼠舌黏膜癌变过程中的表达

    Institute of Scientific and Technical Information of China (English)

    刘曼; 宿颖; 蓝爱仙; 张辛燕; 孙正

    2014-01-01

    目的:检测Krüppel样因子5(Krüppel-like factor 5,KLF5)在小鼠舌黏膜癌变模型中的表达,探讨KLF5与口腔黏膜癌变的关系。方法将42只 C57BL/6J 小鼠随机分为阴性对照组、4-硝基喹啉-1-氧化物(4NQO)处理组。阴性对照组不做任何处理,4NQO组以4NQO水溶液(50μg/ml)代替饮用水饲养,共16周。实验第24周末处死全部动物,取舌组织进行HE染色及KLF5平均光密度值分析。结果 HE染色显示,对照组小鼠舌背上皮为正常角化的复层鳞状上皮,饮用4NQO水溶液的小鼠舌黏膜上皮出现了不同程度的异常增生及鳞癌。平均光密度测定显示,与正常口腔黏膜上皮相比, KLF5在重度异常增生和鳞癌中的表达明显下降( P<0.01)。结论 KLF5可能在口腔黏膜上皮癌变过程中作为肿瘤抑制基因发挥重要作用。%Objective To examine the expression of KLF5 in 4NQO-induced mouse tongue carcinogenesis. Methods Forty-two C57BL/6J mice were divided into two groups, control group (without any treatment) and 4NQO group, in which the mice were given 4NQO(50μg/ml)in drinking water for 16 weeks. At the end of 24thweek , the mice were sacrificed and their tongues were harvested for HE staining and immunohistochemistry. Results HE staining showed that normal stratified squamous epithelium were observed in the tongues of the control, and mild to severe dysplasia and even to squamous cell carcinoma lesions appeared in the tongues of 4NQO group. Immunohistochemistry results showed that the KLF5 displayed a strong nuclear staining in normal tongue mucosa. The expression of KLF5 markedly decreased in the severe dysplasia to squamous cell carcinomas, which was significantly different with that in the control group ( P < 0. 01 ) . Conclusion KLF5 may serve as a tumor suppressor gene in oral carcinogenesis.

  8. 4NQO诱导大鼠舌黏膜癌变过程中HSF1的表达及意义%Expression and significance of HSF1 in 4NQO-induced rat tongue carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    李传祝; 王飞; 王琼; 刘来奎

    2016-01-01

    Objective: To explore the expression and significance of heat shock factor 1 ( HSF1 ) in 4⁃nitroquinoline 1⁃oxide ( 4NQO) induced rat tongue carcinogenesis. Methods:A total of 80 Wistar rats were randomly divided into two groups. Rats in experi⁃ment group were administered orally with 0.001%⁃0.004%4NQO for 8⁃28 weeks, while rats in the control group were administered with tap water. Then the rats were killed at 8, 16, 20, 24, 28 weeks and their tongues were removed for general observation, histological assessment and HSF1 immunohistochemical staining. Results: Gross changes were observed, including granulations, white patches, verruca, cauliflower⁃like shape leukoplakia and ulcer⁃like changes on the posterior part of the tongue dorsum of experimental group with increasing concentrations and prolonged action of 4NQO. Their corresponding histopathological results ranged from hyperplasia, mild dysplasia (MiDP), moderate dysplasia (MoDP) and severe dysplasia(SDP), in situ carcinoma (ISC) to early invasive carcinoma ( EIC) . The incidence of tongue cancer in rats treated with 4NQO for 8, 16, 20, 24, 28 weeks was 0, 20.0%, 50.0%, 66.70% and 100%. Rat tongue mucosa epithelium of the control rats was almost negative or low for HSF1 staining. But with the aggravation of the tongue mucosal dysplasia, the positive expression of HSF1 of the experimental rats increased obviously. HSF1 was distributed through⁃out the entire cancer nest in carcinoma in situ. The expression of HSF1 was low in cancer epithelium of well⁃differentiated squamous cell carcinoma, while high in carcinoma stromal fibroblasts. Conclusions:4NQO drinking water can induce rat tongue carcinogenesis, wich helps to successfully establish the rat tongue carcinogenesis model and HSF1 may play a key role in the development of the cancer.%目的:探讨热休克因子1( HSF1)在4⁃硝基喹啉⁃1⁃氧化物(4NQO)饮水法诱导大鼠舌黏膜癌变过程中

  9. 过氧化氢对小鼠口腔癌发病影响的实验研究%Effect of hydrogen peroxide on 4NQO induced oral carcinogenesis

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    王晓昆; 孙正; 张辛燕; 葛丽华; 苗聪聪; 田振川

    2012-01-01

    Objective To examine Ihe expression oi Inriz, Gs1-tt,H0-1 in 4lN(()U-induced oral cancer oi mouse and ihe effecl on ihe carcinogenesis of 4NQO-induced oral cancer. Methods A lolal of 190 male C57BL/6J mice ( 8 weeks old) were divided inlo five groups,Group A and B serving as negalive and posilive conlrol,Group C,D and E Irealed wilh hydrogen peroxide. The negalive conlrol,Group C,D and E were Irealed wilh 0. 005% 4NQO for 16 weeks, and ihen ihe longue of ihese 4 groups were topically smeared wilh hydrogen peroxid 3 limes a week for 8 weeks. Al ihe end of 24 weeks,all ihe animals were sacrificed. The longue was harvested and examined for ihe presence of macroscopic alterations and for hislopathology. Results During ihe progression of oral carcinogenesis, Nrf2, GST-tt and HOI was over expressed from the premalignanl to malignanl stage. Conclusion Oxidalive damage caused by hydrogen peroxide further promoled the carcinogenesis of 4NQO-induced oral cancer.%目的 检测氧化应激相关基因Nrf2、GST-π、HO1在4NQO小鼠舌癌标本中的表达水平,分析氧化损伤对4NQO诱导的小鼠口腔癌的促进作用.方法 190只8周龄雄性C57BL/6J小鼠随机分为阴性对照组、阳性对照组、6%、15%和30%过氧化氢处理组.阴性对照组不做任何处理,其余4组以0.005% 4NQO诱癌16周后,分别用水(阳性对照组)和6%、15%、30%的过氧化氢涂抹小鼠舌部,每周3次,共8周.第24周末处死全部动物,取舌组织进行组织病理学分析及免疫组化染色.结果 在粘膜从正常到异常增生、再到癌变的过程中,Nrf2、GST-π和HO1的表达持续升高,并且30%过氧化氢组中重度异常增生和癌变的组织中上述三者的积分光密度值显著高于阳性对照组(P<0.01);6%和15%组中,GST-π的积分光密度值均显著高于阳性对照组(P<0.05),Nrf2和HO1的积分光密度值与阳性对照组无统计学差异.结论 过氧化氢造成的氧化损伤进一步促进了4NQO小鼠口腔癌的发展.

  10. Ultramicrostructural Observation on Epithelial Cell disdifferentiation in Rat Tongue Carcinogenesis Induced by 4NQO%4NQO诱发大鼠舌癌变细胞分化异常的超微结构观察

    Institute of Scientific and Technical Information of China (English)

    刘兴坤; 何荣根; 陈万涛; 张志愿; 周曾同; 周晓健

    2001-01-01

    Objective To clarify epithelial cell ultramicrostructure changesin oral carcinogenesis. Method The epithelial cell ultramicrostructures in tongue carcinogenesis induced by 4-nitroquinoline-1-oxide (4NQO) were observed by transmission electron microscope. Results With the progress of oral carcinogenesis, regular changes of epithelial cell were showed: decrease in tonofibril, keratohyaline granules, desmosome; and increase in mitochondria. The basement membrane was broken in some severe dysplasia (sDP) and was broken through by parts of cell processes in in situ carcinoma (ISC). Conclusion Oral carcinogenesis is a multistep process. Epithelial cell aberrant differentiation is showed by a decrease in the synthetic products of epithelium cell.%目的 探讨4-硝基喹啉-1-氧化物(4NQO)诱发大鼠舌癌变细胞分化异常的超微结构及其变化规律。方法 口服4NQO诱发大鼠舌粘膜癌变,透射电镜动态观察癌变过程中细胞的超微结构变化。结果 随大鼠舌癌变进展,鳞状上皮细胞浆、核、细胞间连接、基底膜等发生规律性变化。其中张力原纤维、桥粒、角质颗粒呈逐渐减少趋势,线粒体则逐渐增多;部分重度异常增生上皮已发生基底膜断裂,原位癌细胞有个别已突破基底膜。结论 口腔癌变是一个渐变过程,鳞状上皮分化异常主要表现为合成产物减少和增殖代谢活跃细胞器增多。电镜观察基底膜可以早期发现癌变。

  11. Construction of SD rats' oral squamous cell carcinoma model under the barrier environment induced by drinking 4NQO solution%屏障环境下建立4NQO饮水诱导SD大鼠口腔鳞癌模型

    Institute of Scientific and Technical Information of China (English)

    廖鹏程; 张绪; 谭红; 邓婷婷; 聂敏海

    2015-01-01

    目的 建立与人类发病机理相似的大鼠口腔癌前病变与鳞癌模型,为进一步研究口腔鳞癌的发生发展机制提供实验对象.方法 在屏障环境下将质量分数为0.004%的4-硝基喹啉-1-氧化物(4-nitro-quinoline-1-oxide,4NQO)水溶液,作为饮水给予大鼠自行饮用,观察大鼠口腔黏膜的变化,并在第10、14、18、22、24周分5批处死,采集口腔黏膜标本,确定病理分级及病变性质.结果 82只有效实验大鼠中:①舌正常黏膜25.6%(21/82)、上皮单纯增生25.6% (21/82)、轻度异常增生17.1% (14/82)、中度异常增生9.8% (8/82)、重度异常增生2.4%(2/82)、鳞癌19.5% (16/82);②腭正常黏膜20.7%(17/82)、上皮单纯增生23.2% (19/82)、轻度异常增生24,4% (20/82)、中度异常增生14.6% (12/82)、重度异常增生7.3% (6/82)、鳞癌9.8% (8/82).实验组病理分级结果采用等级资料的多个独立样本的Kruskal-Wallis秩和检验,舌黏膜(x2=20.738,P<0.005)、腭黏膜(x2=15.003,P<0.005),结果分布差异均有统计学意义.结论 该模型可排除其它外界因素对实验结果的干扰,实验效果明确,是理想的研究口腔鳞癌发生发展机制的动物模型.

  12. 4-Nitroquinoline-1-oxide effects human lung adenocarcinoma A549 cells by regulating the expression of POLD4

    OpenAIRE

    HUANG, QIN-MIAO; ZENG, YI-MING; ZHANG, HUA-PING; LV, LIANG-CHAO; YANG, DONG-YONG; LIN, HUI-HUANG

    2016-01-01

    The aim of the present study was to explore the expression of POLD4 in human lung adenocarcinoma A549 cells under 4-nitroquinoline-1-oxide (4NQO) stimulation to investigate the role of POLD4 in smoking-induced lung cancer. The lung cancer A549 cell line was treated with 4NQO, with or without MG132 (an inhibitor of proteasome activity), and subsequently the POLD4 level was determined by western blot analysis. Secondly, the cell sensitivity to 4NQO and Taxol was determined when the POLD4 expres...

  13. The molecular features of tongue epithelium treated with the carcinogen 4-nitroquinoline-1-oxide and alcohol as a model for HNSCC.

    Science.gov (United States)

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

    2013-11-01

    Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer affecting humans worldwide. To determine the potential mechanisms by which chronic tobacco and alcohol abuse lead to HNSCC of the oral cavity, we have used both the 4-nitroquinoline-1-oxide (4-NQO) murine oral carcinogenesis and the Meadows-Cook alcohol models. In this study, we treated mice with 4-NQO in drinking water for 10 weeks and then administered 20% (w:v) ethanol (EtOH) for another 10 weeks. We observed increased levels and/or activation of signaling proteins [p38 mitogen-activated protein kinase (MAPK), β-catenin and Erk 1/2] that are typically altered during HNSCC initiation in humans. We found that EtOH administration alone increased the expression of p38 MAPK but not Erk 1/2 MAPK. Total β-catenin levels in the tongues increased by 2- to 3-fold after 4-NQO treatment, with or without EtOH. However, EtOH combined with 4-NQO reduced phosphorylated β-catenin levels, whereas 4-NQO treatment alone did not. These data implicate EtOH as a regulator of β-catenin signaling in this HNSCC model. We also utilized K14-CreER(TAM); ROSA26 mice to mark permanently stem/progenitor cells in the tongue epithelia. We found that 4-NQO alone and 4-NQO plus EtOH treatment resulted in massive, horizontal expansion of stem/progenitor cell populations arising from single stem cells in the basal layer of the epithelia. This expansion is consistent with carcinogen-associated, symmetric division of stem/progenitor cells. Our data suggest that specific therapeutic targets for prevention of HNSCC of the oral cavity associated with both alcohol and tobacco use are p38 MAPK and β-catenin.

  14. Evaluation the effect of topical and systemic celecoxib on serum antioxidant in induction of tongue neoplasm in rat

    Directory of Open Access Journals (Sweden)

    Fatemeh Arbabi-Kalati

    2010-11-01

    Full Text Available Background: Oral cancer is one of the ten most frequent cancers worldwide. Reactive oxygen species (ROS, may play a key role in human cancer development. Inflammation occurs in cancers and increases oxidative stress agent COX2 over expression in oral premalignant lesions. Several studies showed COX2 inhibitors con improve antioxidant system. The aim of this study is the evaluation the effect of topical and systemic celecoxib on serum antioxidant in induction of tongue neoplasm in rat. Materials and Method: Fifty male Sprague Dawley adult 3-3.5 months' old rats were used as animal model in this study. The tongue SCC was induced by a daily administration of 30 ppm 4-nitroquinoline 1-oxide (4-NQO, in drinking water, for 8 months. The rats in case groups received dietary or topical CCB. CCB powder was added to powdered basal diet and e ach rat received CCB with daily food. Adhesive Gels were prepared by mixing the base plasty with oral paste including two different dose of CCB. These groups include: group A» 30 ppm 4-NQO treatment; group B» 30 ppm 4-NQO+dietary CCB treatment; group C» 30 ppm 4-NQO+topical low dose CCB treatment; group D» 30 ppm 4NQO+high dose topical CCB treatment and group E» dietary CCB as control+water. Results: Statistical analysis showed significant differens between groups in total antioxidant, hemoglobin and nutrophilic count.Conclusion: Topical CCB can use as adjuvant treatment for premalignant lesions

  15. 4-nitroquinoline-1-oxide-induced mutagen sensitivity and risk of cutaneous melanoma: a case-control analysis.

    Science.gov (United States)

    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.

  16. 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。

  17. 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

  18. 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.

  19. Cytologic Effects of Air Force Chemicals

    Science.gov (United States)

    1980-11-01

    amounts of methylated guanine residues in the DNA. The DNA samples were hydrolyzed and chromatographed using high pressure liquid chromatography ( HPLC ...induced in freshly isolated lymphocytes by four chemicals, 4NQO, MMS, HN2 and mitomycin C (MMC). The differences in DRS are probably due to the chemical

  20. 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.

  1. 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.

  2. 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.

  3. Oxidative DNA damage is a preliminary step during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide.

    Science.gov (United States)

    Miranda, Sandra Regina; Noguti, Juliana; Carvalho, Juliana Gonçalves; Oshima, Celina Tijuko Fujiyama; Ribeiro, Daniel Araki

    2011-04-01

    The aim of this study was to investigate oxidative DNA damage during 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis. For this purpose, male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution through their drinking water for 4, 12, and 20 weeks. Ten animals were used as negative control. The alkaline Comet assay modified with lesion-specific enzymes was used to detect single and double strand breaks, labile sites (SBs), and oxidised purines and pyrimidines. Although no histopathological abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure, oxidative DNA damage was detected in the 'normal' oral epithelium. In pre-neoplastic lesions and squamous cell carcinomas induced after 12 and 20 weeks following carcinogen exposure, respectively, oxidative DNA damage was also increased (P < 0.05) when compared to negative control. In conclusion, our results suggest that oxidative DNA damage is an early event during multistep carcinogenesis assay induced by 4NQO. This kind of approach should be considered to persons with high risk of oral cancer, such as in smokers or alcohol consumers.

  4. Synergistic effect of isopropanol on induction of mitotic aberrations in Allium cepa

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, S. [DynCorp, Cincinnati, OH (United States); Meier, J.R.; Smith, M.K. [Environmental Protection Agency, Cincinnati, OH (United States); Torsella, J. [Oak Ridge Inst. of Science and Education, Cincinnati, OH (United States)

    1995-12-31

    Soil from a site heavily contaminated with polychlorinated biphenyls and several other organic and inorganic compounds was remediated by treatment with a mobile solvent extraction system. The genotoxicity of the soil, as measured by the induction of anaphase aberrations in Allium cepa root tip cells, increased after the remediation process. This increase appeared to be due to synergism between the residual solvent and genotoxic components not removed by the solvent extraction process. The purpose of the present study was to determine whether isopropanol, at concentrations similar to residual amounts following remediation, induced a synergistic response with the known clastogen, 4-nitroquinoline n-oxide (4-NQO). Bulblets of Allium cepa (common onion) were exposed for 24 h to varying concentrations of isopropanol combined with 0.10 mg/14-NQO in aqueous solution. The root tips were examined for mitotic index (MI), and cells in late anaphase/early telophase were scored for mitotic aberrations (MA, i.e., bridges, fragments, and lagging chromosomes). MI and MA frequencies were transformed by the arcsin square root function prior to statistical analysis (ANOVA). Isopropanol by itself did not induce MA and did not affect the Ml, either alone or in combination with 4-NQO. However, isopropanol enhanced the 4-NQO induced MA response by 1.4 fold at 1.0 mg/ml (p-value = 0.13) and 2.0 fold at 1.2 mg/ml (p-value = 0.006). Lower concentrations of 0.3 and 0.1 mg/ml isopropanol had no effect. The results demonstrate that residual solvents can increase the genotoxicity of soils, presumably as a result of enhancing the bioavailability of genotoxic components.

  5. 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.

  6. 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

  7. Estudo da expressão de proteínas da via Wnt e Hedgehog na carcinogênese bucal em camundongos wild-type e knockout para o gene da galectina-3

    OpenAIRE

    Santos, Débora de Oliveira

    2013-01-01

    O carcinoma epidermóide (CE) é a neoplasia mais comum da cavidade oral e a cada ano mais de 300.000 novos casos são diagnosticados em todo o mundo. Para compreender as alterações moleculares associadas ao seu desenvolvimento, bem como para identificar marcadores diagnósticos e prognósticos para CE, muitos trabalhos têm utilizado modelos de carcinogênese bucal em animal desafiados com o carcinógeno 4-Nitroquinoline-1-Oxide (4NQO). A galectina-3 (Gal-3) é uma proteína pertencente à família das ...

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

    Science.gov (United States)

    Del-Toro-Sánchez, Carmen Lizette; Bautista-Bautista, Nereyda; Blasco-Cabal, José Luis; Gonzalez-Ávila, Marisela; Gutiérrez-Lomelí, Melesio; Arriaga-Alba, Myriam

    2014-01-01

    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. PMID:25152760

  9. The effect of desalivation on the malignant transformation of the tongue epithelium and associated stromal myofibroblasts in a rat 4-nitroquinoline 1-oxide-induced carcinogenesis model.

    Science.gov (United States)

    Vered, Marilena; Grinstein-Koren, Osnat; Reiter, Shoshana; Allon, Irit; Dayan, Dan

    2010-08-01

    The aim of our study was to analyse desalivated rat tongue epithelium for histopathological changes, proliferating cell nuclear antigen (PCNA), and epithelium-associated stromal myofibroblasts [SMF; alpha-smooth muscle actin (alphaSMA)] following 0.001% 4-nitroquinoline 1-oxide (4NQO) administration in drinking water. Results were compared with those of identically treated but salivated specimens. 4NQO was administered for 7, 14, 22 and 28 weeks. Tongue length was divided into anterior, middle and posterior 'thirds'. The histopathological changes per 'third' were scored as normal epithelium, hyperplasia, dysplasia, carcinoma-in-situ, and superficial and invasive carcinoma. The PCNA and alphaSMA stains were assessed by a point-counting method. At all time points, the histopathological changes in the anterior and middle thirds were higher in the desalivated than in the salivated group (P 0.05). PCNA scores were significantly lower in the desalivated vs. the salivated group at almost all time points and tongue thirds (P tongue epithelium in the early stages. PCNA cannot be regarded as a marker of proliferation and probably contributes to this process by other mechanisms. Emergence of SMF seems to be highly dependent on growth factors from saliva in addition to factors from cancerous cells.

  10. 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.

  11. Absence of genotoxic effects of the chalcone (E)-1-(2-hydroxyphenyl)-3-(4-methylphenyl)-prop-2-en-1-one) and its potential chemoprevention against DNA damage using in vitro and in vivo assays

    Science.gov (United States)

    2017-01-01

    The chalcone (E)-1-(2-hydroxyphenyl)-3-(4-methylphenyl)-prop-2-en-1-one), or 2HMC, displays antileishmanial, antimalarial, and antioxidant activities. The aim of this study was to investigate the cytotoxic, genotoxic, mutagenic, and protective effects of 2HMC using the Ames mutagenicity test, the mouse bone marrow micronucleus test, and the comet assay in mice. In the assessment using the Ames test, 2HMC did not increase the number of His+ revertants in Salmonella typhimurium strains, demonstrating lack of mutagenicity. 2HMC showed no significant increase in micronucleated polychromatic erythrocyte frequency (MNPCE) in the micronucleus test, or in DNA strand breaks using the comet assay, evidencing absence of genotoxicity. Regarding cytotoxicity, 2HMC exhibited moderate cytotoxicity in mouse bone marrow cells by micronucleus test. 2HMC showed antimutagenic action in co-administration with the positive controls, sodium azide (SA) and 4-nitroquinoline-1-oxide (4NQO), in the Ames test. Co-administered and mainly pre-administered with cyclophosphamide (CPA), 2HMC caused a decrease in the frequency of MNPCE using the micronucleus test and in DNA strand breaks using the comet assay. Thus, 2HMC exhibited antimutagenic and antigenotoxic effects, displaying a DNA-protective effect against CPA, SA, and 4NQO carcinogens. In conclusion, 2HMC presented antimutagenic, antigenotoxic and moderate cytotoxic effects; therefore it is a promising molecule for cancer prevention. PMID:28207781

  12. 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.

  13. 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.

  14. 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.

  15. 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

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

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    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 .

  17. Modulation of genotoxicity of oxidative mutagens by glycyrrhizic acid from Glycyrrhiza glabra L.

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    Prabhjit Kaur

    2012-01-01

    Full Text Available Background: The chemopreventive effects of certain phytoconstituents can be exploited for their use as functional foods, dietary supplements and even as drugs. The natural compounds, acting as anti-genotoxic and free radical scavenging compounds, may serve as potent chemopreventive agents. These can inhibit DNA modulatory activities of mutagens and help preventing pathological processes. Objectives: Present study on Glycyrrhiza glabra L., a promising medicinal plant, widely used in traditional medicine, focused on the bioassay-guided fractionation of its extracts for the isolation of certain phytochemicals with anti-genotoxic potential against oxidative mutagens. Materials and Methods: The methanol extract of Glycyrrhiza glabra rhizomes was subjected to column chromatography, and isolated fraction was evaluated for its anti-genotoxic and antioxidant potential using SOS chromotest, Comet assay, and DPPH radical scavenging assay. Results: GLG fraction, which was characterized as Glycyrrhizic acid, inhibited the genotoxicity of oxidative mutagens viz., H 2 O 2 and 4NQOquite efficiently. In SOS chromotest, using E.coli PQ37 tester strain, it inhibited induction factor induced by H 2 O 2 and 4NQO by 75.54% and 71.69% at the concentration of 121.46 μM,respectively. In Comet assay, it reduced the tail moment induced by H 2 O 2 and 4NQO by 70.21% and 69.04%, respectively, at the same concentration in human blood lymphocytes. The isolated fraction also exhibited DPPH free radical scavenging activity and was able to scavenge 85.95% radicals at a concentration of 120 μM. Conclusion: Glycyrrhizic acid is a potential modulator of genotoxins as well as efficient scavenger of free radicals.

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

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    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.

  19. Antimutagenicity of an acetone extract of yogurt.

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    Nadathur, S R; Gould, S J; Bakalinsky, A T

    1995-04-01

    Reconstituted non-fat dry milk powder, fermented by a mixture of Streptococcus thermophilus CH3 and Lactobacillus bulgaricus 191R to produce yogurt, was freeze-dried and extracted in acetone. After evaporation of the acetone, the extract was dissolved in dimethyl sulfoxide (DMSO) and tested for antimutagenicity. In the Ames test, significant dose-dependent activity was observed against N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 4-nitro-quinoline-N-oxide (4NQO), 3,2'-dimethyl-4-aminobiphenyl (DMAB), 9,10-dimethyl-1,2-benz[a]anthracene (DMBA), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole acetate (Trp-P-2). Weak activity was observed against 1,2,7,8-diepoxyoctane (DEO), and no activity was observed against methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS), or aflatoxin B1 (AFB1). In a related assay (Saccharomyces cerevisiae D7), significant antimutagenic activity was detected against MNNG and 4NQO. Activity against the experimental colon carcinogens MNNG and DMAB was examined further, as assayed in the Ames test (Salmonella typhimurium TA100). Compounds responsible for both activities were less soluble in aqueous solutions than in DMSO. Adjustment of yogurt pH to 3, 7.6, or 13 prior to freeze-drying and acetone extraction did not significantly alter the amount of anti-MNNG activity recovered. In contrast, extractability of anti-DMAB activity was significantly greater at acidic pH. Conjugated linoleic acid, a known dairy anticarcinogen, failed to inhibit mutagenesis caused by either mutagen, suggesting that other yogurt-derived compound(s) are responsible. Unfermented milk was treated with lactic acid, yogurt bacteria without subsequent growth, or both, to determine if formation of antimutagenic activity required bacterial growth. Extracts of the milk treatments exhibited the same weak antimutagenicity observed in unfermented milk, approximately 2.5-fold less than in the yogurt extracts, suggesting that antimutagenic activity is associated with bacterial

  20. Assessment of the mutagenic potential of Cr(VI) in the oral mucosa of Big Blue® transgenic F344 rats.

    Science.gov (United States)

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

    2015-08-01

    Exposure to high concentrations of hexavalent chromium [Cr(VI)] in drinking water was associated with an increased incidence of oral tumors in F344 rats in a 2-year cancer bioassay conducted by the National Toxicology Program. These tumors primarily occurred at 180 ppm Cr(VI) and appeared to originate from the gingival mucosa surrounding the upper molar teeth. To investigate whether these tumors could have resulted from a mutagenic mode of action (MOA), a transgenic mutation assay based on OECD Test Guideline 488 was conducted in Big Blue(®) TgF344 rats. The mutagenic oral carcinogen 4-nitroquinoline-1-oxide (4-NQO) served as a positive control. Mutant frequency was measured in the inner gingiva with adjacent palate, and outer gingiva with adjacent buccal tissue. Exposure to 10 ppm 4-NQO in drinking water for 28 days increased mutant frequency in the cII transgene significantly, from 39.1 ± 7.5 × 10(-6) to 688 ± 250 × 10(-6) in the gingival/buccal region, and from 49.8 ± 17.8 × 10(-6) to 1818 ± 362 × 10(-6) in the gingival/palate region. Exposure to 180 ppm Cr(VI) in drinking water for 28 days did not significantly increase the mutant frequency in the gingival/buccal (44.4 ± 25.4 × 10(-6)) or the gingival/palate (57.8 ± 9.1 × 10(-6)) regions relative to controls. These data indicate that high (∼180,000 times expected human exposure), tumorigenic concentrations of Cr(VI) did not significantly increase mutations in the gingival epithelium, and suggest that Cr(VI) does not act by a mutagenic MOA in the rat oral cavity.

  1. 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

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    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.

  2. Prevention of Carcinogen-Induced Oral Cancer by Sulforaphane.

    Science.gov (United States)

    Bauman, Julie E; Zang, Yan; Sen, Malabika; Li, Changyou; Wang, Lin; Egner, Patricia A; Fahey, Jed W; Normolle, Daniel P; Grandis, Jennifer R; Kensler, Thomas W; Johnson, Daniel E

    2016-07-01

    Chronic exposure to carcinogens represents the major risk factor for head and neck squamous cell carcinoma (HNSCC). Beverages derived from broccoli sprout extracts (BSE) that are rich in glucoraphanin and its bioactive metabolite sulforaphane promote detoxication of airborne pollutants in humans. Herein, we investigated the potential chemopreventive activity of sulforaphane using in vitro models of normal and malignant mucosal epithelial cells and an in vivo model of murine oral cancer resulting from the carcinogen 4-nitroquinoline-1-oxide (4NQO). Sulforaphane treatment of Het-1A, a normal mucosal epithelial cell line, and 4 HNSCC cell lines led to dose- and time-dependent induction of NRF2 and the NRF2 target genes NQO1 and GCLC, known mediators of carcinogen detoxication. Sulforaphane also promoted NRF2-independent dephosphorylation/inactivation of pSTAT3, a key oncogenic factor in HNSCC. Compared with vehicle, sulforaphane significantly reduced the incidence and size of 4NQO-induced tongue tumors in mice. A pilot clinical trial in 10 healthy volunteers evaluated the bioavailability and pharmacodynamic activity of three different BSE regimens, based upon urinary sulforaphane metabolites and NQO1 transcripts in buccal scrapings, respectively. Ingestion of sulforaphane-rich BSE demonstrated the greatest, most consistent bioavailability. Mucosal bioactivity, defined as 2-fold or greater upregulation of NQO1 mRNA, was observed in 6 of 9 evaluable participants ingesting glucoraphanin-rich BSE; 3 of 6 ingesting sulforaphane-rich BSE; and 3 of 9 after topical-only exposure to sulforaphane-rich BSE. Together, our findings demonstrate preclinical chemopreventive activity of sulforaphane against carcinogen-induced oral cancer, and support further mechanistic and clinical investigation of sulforaphane as a chemopreventive agent against tobacco-related HNSCC. Cancer Prev Res; 9(7); 547-57. ©2016 AACR.

  3. Antimutagenic activity of a novel ascorbic derivative, disodium isostearyl 2-O-L-ascorbyl phosphate.

    Science.gov (United States)

    Hisama, Masayoshi; Matsuda, Sanae; Shibayama, Hiroharu; Iwaki, Masahiro

    2008-06-01

    A novel amphiphilic vitamin C derivative, disodium isostearyl 2-O-L-ascorbyl phosphate (VCP-IS-2Na) possessing an alkyl chain of C(18) to a stable ascorbate derivative sodium L-ascorbic acid 2-phosphate (VCP-Na), was synthesized and evaluated as an anti-mutagen with suppressive effect on SOS-inducing activity on mutagen in the Salmonella typhimurium TA1535/pSK1002 umu test. VCP-IS-2Na was assayed with chemical mutagens, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide (furylfuramide) and 4-nitroquinolin 1-oxide (4NQO), which do not require liver metabolizing enzymes. VCP-IS-2Na at a concentration of 0.40 micromol/ml suppressed 66.2%, 54.7% and 60.2% of the SOS-inducing activity on MNNG, furylfuramide, and 4NQO, and the 50% inhibitory dose value (ID(50)) was 0.12 micromol/ml, 0.26 micromol/ml, and 0.17 micromol/ml, respectively. In addition, VCP-IS-2Na was assayed with 2-aminoanthracene (2AA) and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), which require liver metabolizing enzymes. To study the structure-activity relationship, L-ascorbic acid (VC) and VCP-Na were also assayed with all mutagens. VCP-IS-2Na, suppressed the chemical and physical mutagens-induced SOS response greater than VC and VCP-Na in the umu test. Also, the antimutagenic activities of VCP-IS-2Na, VC, and VCP-Na against MNNG and Trp-P-1 were assayed by the Ames test using the S. typhimurium TA100 strain. In summary, this research suggests that VCP-IS-2Na showed potent antimutagenic effects against chemical mutagens and UV irradiation.

  4. 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

  5. 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

  6. 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.

  7. Fructose-1,6-bisphosphatase mediates cellular responses to DNA damage and aging in Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Kitanovic, Ana [Institut fuer Pharmazie und Molekulare Biotechnologie, Ruprecht-Karls-Universitaet Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg (Germany); Woelfl, Stefan [Institut fuer Pharmazie und Molekulare Biotechnologie, Ruprecht-Karls-Universitaet Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg (Germany)]. E-mail: wolfl@uni-hd.de

    2006-02-22

    Response to DNA damage, lack of nutrients and other stress conditions is an essential property of living systems. The coordinate response includes DNA damage repair, activation of alternate biochemical pathways, adjustment of cellular proliferation and cell cycle progression as well as drastic measures like cellular suicide which prevents proliferation of severely damaged cells. Investigating the transcriptional response of Saccharomyces cerevisiae to low doses of the alkylating agent methylmethane sulfonate (MMS) we observed induction of genes involved in glucose metabolism. RT-PCR analysis showed that the expression of the key enzyme in gluconeogenesis fructose-1,6-bisphosphatase (FBP1) was clearly up-regulated by MMS in glucose-rich medium. Interestingly, deletion of FBP1 led to reduced sensitivity to MMS, but not to other DNA-damaging agents, such as 4-NQO or phleomycin. Reintroduction of FBP1 in the knockout restored the wild-type phenotype while overexpression increased MMS sensitivity of wild-type, shortened life span and increased induction of RNR2 after treatment with MMS. Deletion of FBP1 reduced production of reactive oxygen species (ROS) in response to MMS treatment and in untreated aged cells, and increased the amount of cells able to propagate and to form colonies, but had no influence on the genotoxic effect of MMS. Our results indicate that FBP1 influences the connection between DNA damage, aging and oxidative stress through either direct signalling or an intricate adaptation in energy metabolism.0.

  8. 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.

  9. Preliminary assessment of mutagenic and anti-mutagenic potential of some aminoalkanolic derivatives of xanthone by use of the Vibrio harveyi assay.

    Science.gov (United States)

    Słoczyńska, Karolina; Waszkielewicz, Anna Maria; Marona, Henryk

    2014-07-01

    The Vibrio harveyi assay was used to evaluate mutagenic and anti-mutagenic effects of four new aminoalkanolic derivatives of xanthone with anticonvulsant activity, to select the potentially safe compounds for further in vivo studies in animal models. The study showed that at a concentration of 40 ng/ml the test compounds were not mutagenic. Additionally, two of the investigated compounds, namely the (R,S)-N-methyl-1-amino-2-propanol derivative of 6-methoxyxanthone (compound III) and the (R)-N-methyl-2-amino-1-butanol derivative of 7-chloroxanthone (compound IV) were strong inhibitors of the mutagenicity induced by 4-nitroquinoline-N-oxide (4-NQO) in V. harveyi strains BB7M and BB7XM. The inhibition percentages for compound IV were 49 (in BB7M) and 69 (in BB7XM), whereas for compound III these percentages were 47 (in BB7M) and 42 (in BB7XM), respectively. The present study demonstrates that four bioactive derivatives of xanthone display no mutagenic activity in the V. harveyi assay. In addition, compounds III and IV demonstrated considerable anti-mutagenic activity in this test. Based on the results obtained here, these compounds could be selected for further studies in animal models, while compounds III and IV should be tested further for their anti-mutagenic properties.

  10. Bmi1-positive cells in the lingual epithelium could serve as cancer stem cells in tongue cancer.

    Science.gov (United States)

    Tanaka, Toshihiro; Atsumi, Naho; Nakamura, Naohiro; Yanai, Hirotsugu; Komai, Yoshihiro; Omachi, Taichi; Tanaka, Kiyomichi; Ishigaki, Kazuhiko; Saiga, Kazuho; Ohsugi, Haruyuki; Tokuyama, Yoko; Imahashi, Yuki; Hisha, Hiroko; Yoshida, Naoko; Kumano, Keiki; Okazaki, Kazuichi; Ueno, Hiroo

    2016-12-22

    We recently reported that the polycomb complex protein Bmi1 is a marker for lingual epithelial stem cells (LESCs), which are involved in the long-term maintenance of lingual epithelial tissue in the physiological state. However, the precise role of LESCs in generating tongue tumors and Bmi1-positive cell lineage dynamics in tongue cancers are unclear. Here, using a mouse model of chemically (4-nitroquinoline-1-oxide: 4-NQO) induced tongue cancer and the multicolor lineage tracing method, we found that each unit of the tumor was generated by a single cell and that the assembly of such cells formed a polyclonal tumor. Although many Bmi1-positive cells within the tongue cancer specimens failed to proliferate, some proliferated continuously and supplied tumor cells to the surrounding area. This process eventually led to the formation of areas derived from single cells after 1-3 months, as determined using the multicolor lineage tracing method, indicating that such cells could serve as cancer stem cells. These results indicate that LESCs could serve as the origin for tongue cancer and that cancer stem cells are present in tongue tumors.

  11. Estudo da expressão de galectina-3 em carcinomas de língua de camundongos Study of the galectin-3 expression in tongue carcinomas of mice

    Directory of Open Access Journals (Sweden)

    Paulo Rogério de Faria

    2008-06-01

    Full Text Available INTRODUÇÃO: A galectina-3 (Gal-3 é uma lectina de mamíferos ligante de resíduos b-galactosídeos. Numerosos estudos têm mostrado que a Gal-3 apresenta importantes papéis na biologia tumoral, atuando em fenômenos como apoptose, metástase e transformação maligna. No entanto, em carcinomas de cabeça e pescoço, a real significância da sua expressão ainda é pouco compreendida. OBJETIVO: O objetivo deste estudo foi avaliar a expressão de Gal-3 em tumores de língua induzidos experimentalmente em camundongos desafiados com o carcinógeno 4-nitroquinolona-1-óxido (4NQO. MATERIAL E MÉTODOS: Quarenta e dois camundongos C57BL/6, machos, foram desafiados com 4NQO na água de beber por 16 semanas e sacrificados em diferentes períodos depois do tratamento. Após o sacrifício, as línguas foram removidas, processadas, coradas por hematoxilina e eosina (HE e microscopicamente analisadas quanto à presença de carcinoma. Ensaio imuno-histoquímico para detecção do antígeno Gal-3 e análise descritiva da sua expressão nos tumores induzidos foram realizados. RESULTADOS: Ao final do experimento, foram produzidos 15 tumores. No tecido epitelial não-neoplásico, forte imunorreatividade foi observada apenas na camada parabasal. Nas camadas mais superficiais a intensidade de marcação foi mais fraca, e na camada basal variou de ausente a fraca. Todos os carcinomas bem diferenciados exibiram fraca marcação, exceto nas áreas queratinizantes. No único caso de carcinoma pouco diferenciado, forte imunorreatividade para Gal-3 foi observada. CONCLUSÃO: Nossos resultados descritivos mostram que a transformação maligna é acompanhada de redução da intensidade de expressão da Gal-3 e que o aumento da sua expressão com a perda da diferenciação neoplásica sugere a sua vinculação com agressividade tumoral.BACKGROUND: Galectin-3 (Gal-3 is a b-galactoside-binding mammalian lectin. Numerous studies have demonstrated that Gal-3 plays an

  12. 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.

  13. 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.

  14. 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.

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

    Science.gov (United States)

    Liu, Yu-Ching; Ho, Heng-Chien; Lee, Miau-Rong; Lai, Kuang-Chi; Yeh, Chung-Min; Lin, Yueh-Min; Ho, Tin-Yun; Hsiang, Chien-Yun; Chung, Jing-Gung

    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 2h 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.

  16. 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.

  17. 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.

  18. Ultraviolet light photobiology of the protozoan Tetrahymena pyriformis and chemical reactivation of DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Wheeler, J.S.

    1988-01-01

    The tunable dye laser was developed in order to perform UV-B and UV-C (254-320 nm) action spectra studies on several different organisms. Using the laser, action spectra studies have been performed for Escherichia coli, Saccharomyces, Chlamydomonas, Caenorhabditis elegans, Paramecium, and Tetrahymena pyriformis. Studies generally indicate increasing LD{sub 50} values with increasing wavelength. Two notable findings were made: (1) The action spectra does not follow the DNA absorption spectra at 280, 290 and 295 nm; (2) The repair competent/repair defective sensitization factor does not remain constant throughout the wavelength region. In addition it was found that the repair defective strain of E. coli, Bs-1, showed an increase in survival with increasing UV irradiation, at certain dose levels. Further experiments were designed to better characterize the reactivation. Tetrahymena were exposed to UV-C and reactivated with methyl methanesulfonate (MMS) and 4-nitro quinoline oxide (4-NQO). In both cases survival was seen to increase after chemical exposure. Likewise, UV-C was found to reactivate chemical damage (MMS).

  19. 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.

  20. 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.

  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. 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.

  3. 我国近8年非电离辐射研究的概况%Analysis of profiles of non-ionizing radiation in recent 8 years in China

    Institute of Scientific and Technical Information of China (English)

    李文红; 徐翠华; 张京

    2011-01-01

    Objective:To introduce research overview of non ionizing radiation in recent 8 years in China Methods:A total of 40 papers on non-ionizing radiation researches published in Chinese Journal of Radiological Medicine and Protection since 2003 were collected and summarized.Results:We found that the effects of non-ionizing radiation on nervous system,on apoptosis and DNA existed in different degrees.Such as the discovery of electromagnetic radiation of 6h and 7d in rat hippocampal coxⅠ,Ⅱ and mRNA expression were lower compared with sham radiation group,high power microwave radiation can induce rat spermatogenic cell apoptosis,drugs on rat testicular germ cell apoptosis has produced,can up Bcl-2 and low expression of Bax protein,change Bcl-2/Bax ratio;The microwave irradiation after 4-NQO exposure group,50,25μmol/L dose of DNA damage index and the corresponding 4-NQO group had significant difference (P 0.05 or P 0.01).Conclusion:The effects of non-ionizing radiation on human health can not be ignored.%目的:重点介绍我国近8年来非电离辐射研究的概况。方法:收集并归纳了自2003年以来在中华放射医学与防护杂志刊登的40篇有关非电离辐射研究的文章。结果:从刊登的40篇文章中,可以看出非电离辐射对神经系统、对细胞凋亡及DNA损伤有不同程度的影响;发现电磁辐射后6h和7d大鼠海马coxⅠ、Ⅱ和ⅣmRNA表达均较假辐射组降低、高功率微波辐射可诱导大鼠生精细胞凋亡增加,药物对大鼠睾丸生精细胞有产生凋亡的作用,能够上调Bcl-2及下调Bax蛋白的表达,改变了Bcl-2/Bax的比值;有关微波照射后4-NQO染毒组中,50,25μmol/L剂量的DNA损伤指标与相应4-NQO组比较差异均有显著性(P〈0.05或P〈0.01)。结论:从研究结果看出,非电离辐射与人类的生活密不可分,但非电离辐射对人类健康带来的负面影响是不容忽视的。

  4. 金黄地鼠颊黏膜鳞癌动物模型的建立及其生物学特性的研究%Study on establishment of golden hamster buccal squamous carcinoma model for and its biological characteristics

    Institute of Scientific and Technical Information of China (English)

    吕长坤; 万澎波; 马菲菲; 罗春丽; 万雪莲; 王长海

    2013-01-01

    目的建立金黄地鼠颊黏膜鳞癌动物模型,观察其生物学特性。方法40只采用0.05%4-硝基喹啉-1-氧化物(4NQO)涂抹颊黏膜,10只采用自来水涂抹颊黏膜。苏木精-伊红(HE)、转录因子蛋白(Foxm1)免疫组织化学观察第8、12周组织标本。有限稀释法体外传代培养颊黏膜组织标本,观察平板克隆形成率,检测单克隆细胞内细胞角蛋白(C K )和波形蛋白(Vim)表达,染色体分析确定细胞核型。结果第12周时26(84.6%)只颊黏膜病理为原位癌,HE染色、Foxm1免疫组织化学结果表明,符合鳞癌细胞基本特征,CK和Vim免疫组织化学阳性率约为96.0%,染色体为四倍体核型。结论4NQO涂抹诱发金黄地鼠颊黏膜癌变,建立金黄地鼠颊黏膜鳞癌动物模型。%Objective To establish the golden hamster model of buccal squamous carcinoma and observe its biological character-istics .Methods 50 golden hamster were randomly divided into two group :experiment group (n=40) and control group(n=10) . Buccal mucosa of golden hamster were daubed by exposure 4-nitroquinoline-1-oxide (4NQO) in experiment group and tap water in control group .HE staining and immunohistochemistry were used to observe the tissue sample on the 8th and 12th week .The tissue samples of golden hamster buccal-mucosa cancer were used for the in-vitro subculture .Then flat cloning formation rate ,expression of CK and Vim ,and cell karyotype were detected .Results The observations of cell morphology and biology showed that the tissue of buccal squamous carcinoma were conformed to the basic characteristics of squamous carcinoma cell in 26 golden hamster(84 .6% ) after 12 weeks .The positive rate of CK and Vim were 96 .0% by immunohistochemical staining .The Chromosomes were tetraploid karyotype .Conclusion We successfully established the golden hamster model of buccal squamous carcinoma by the daub method of 4NQO .

  5. 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.

  6. 钾离子通道Kv3.4在大鼠颊黏膜癌变中的表达研究%The study of the potassium ion channel Kv 3 .4 in buccal mucosa carcinogenesis of rat

    Institute of Scientific and Technical Information of China (English)

    宋成成; 周俊蛟; 伍宝琴; 聂敏海

    2014-01-01

    Objective To investigate the expression of the Kv3 .4 protein and Kv3 .4 mRNA in various stages of oral carcino‐genesis .Methods The expression of Kv3 .4 protein and Kv3 .4 mRNA were detected by immunohistochemistry (SP method) and RT‐PCR technique respectively in the oral carcinogenesis of SD rat which were induced by 4NQO .Results With the aggravation of the epithelial dysplasia ,Kv3 .4 protein and Kv3 .4 mRNA expression increased gradually .They were strongly positive in oral squa‐mous cell carcinoma .Conclusion The expression of Kv3 .4 protein and Kv3 .4 mRNA levels increased consistently with the aggra‐vation of the epithelial dysplasia .%目的:检测Kv3.4蛋白和Kv3.4 mRNA在大鼠颊黏膜癌变过程中的表达水平。方法采用免疫组织化学(SP)法及RT‐PCR技术检测4NQO诱导的58只SD大鼠颊黏膜癌变各阶段组织中Kv3.4蛋白和Kv3.4 mRNA的表达。结果随上皮异常增生程度的增加,Kv3.4蛋白和Kv3.4 mRNA表达逐渐增加,在口腔鳞状细胞癌中呈强阳性表达。结论在大鼠颊黏膜癌变过程中,Kv3.4蛋白和Kv3.4 mRNA呈现出相似的一致性增高的趋势。

  7. Enhanced stimulation of chromosomal translocations and sister chromatid exchanges by either HO-induced double-strand breaks or ionizing radiation in Saccharomyces cerevisiae yku70 mutants

    Energy Technology Data Exchange (ETDEWEB)

    Fasullo, Michael [Ordway Research Institute, 150 New Scotland Avenue, Albany, NY 12209 (United States)]. E-mail: mfasullo@ordwayresearch.org; St Amour, Courtney [Ordway Research Institute, 150 New Scotland Avenue, Albany, NY 12209 (United States); Zeng Li [Ordway Research Institute, 150 New Scotland Avenue, Albany, NY 12209 (United States)

    2005-10-15

    DNA double-strand break (DSB) repair occurs by homologous recombination (HR) or non-homologous endjoining (NHEJ). In Saccharomyces cerevisiae, expression of both MAT a and MAT{alpha} inhibits NHEJ and facilitates DSB-initiated HR. We previously observed that DSB-initiated recombination between two his3 fragments, his3-{delta}5' and his3-{delta}3'::HOcs is enhanced in haploids and diploids expressing both MAT a and MAT{alpha} genes, regardless of the position or orientation of the his3 fragments. Herein, we measured frequencies of DNA damage-associated translocations and sister chromatid exchanges (SCEs) in yku70 haploid mutants, defective in NHEJ. Translocation and SCE frequencies were measured in strains containing the same his3 fragments after DSBs were made directly at trp1::his3-{delta}3'::HOcs. Wild type and yku70 cells were also exposed to ionizing radiation and radiomimetic agents methyl methanesulfonate (MMS), phleomycin, and 4-nitroquinolone-1-oxide (4-NQO). Frequencies of X-ray-associated and DSB-initiated translocations were five-fold higher in yku70 mutants compared to wild type; however, frequencies of phleomycin-associated translocations were lower in the yku70 haploid mutant. Frequencies of DSB-initiated SCEs were 1.8-fold higher in the yku70 mutant, compared to wild type. Thus, DSB-initiated HR between repeated sequences on non-homologous chromosomes and sister chromatids occurs at higher frequencies in yku70 haploid mutants; however, higher frequencies of DNA damage-associated HR in yku70 mutants depend on the DNA damaging agent.

  8. 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.

  9. Supercoiled DNA folded by nonhistone proteins in cultured mouse carcinoma cells.

    Science.gov (United States)

    Nakane, M; Ide, T; Anzai, K; Ohara, S; Andoh, T

    1978-07-01

    Upon gentle lysis of exponentially growing mouse carcinoma cells FM3A by sodium dodecyl sulfate, DNA was released as a "DNA-protein complex" in a folded conformation. No histones could be detected in the DNA-protein complex. The proteins bound to DNA were found to be composed of several kinds of nonhistone proteins with a molecular weight range of 50,000 to 60,000; they appear to play a key role in stabilizing and maintaining the compact and folded structure of the complex. Removal of the proteins by Pronase or 2-mercaptoethanol produced a more relaxed structure sedimenting about half as fast as the original complex in a neutral sucrose gradient. DNA in the folded complex is supercoiled, as indicated by the characteristic biphasic response of its sedimentation rate to increasing concentration of various intercalating agents, actinomycin D, ethidium bromide and acriflavine, with which the cells were treated before lysis. Pronase- or 2-mercaptoethanol-treated relaxed DNA still possessed the characteristic of closed-circular structure as judged from its response to intercalating agents. Nicking with gamma-ray or 4NQO broke these superhelical turns and relaxed the folded complex to slower sedimenting forms equivalent to the relaxed DNA obtained on treatment with Pronase or 2-mercaptoethanol. Viscometric observations of DNA-protein complex were consistent with the above results. A tentative model for the structure of this DNA-protein complex is proposed in which supercoiled DNA is folded into loops by several kinds of nonhistone proteins. Autoradiographic examination of the complex appeared to support this model.

  10. 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.

  11. 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

  12. 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

  13. Study of oral precancerous lesion and oral cancer by using micro PET/CT%Micro PET/CT在大鼠口腔黏膜癌前病变及口腔癌中的应用

    Institute of Scientific and Technical Information of China (English)

    陈梁; 葛姝云; 李晗卿; 周海文

    2012-01-01

    PURPOSE: To study oral precancerous lesion and oral cancer by using micro PET/CT. METHODS: Thirty-nine SD rats were divided into experimental group and control group. 33 of them were raised with a 4-nitroquinoline-l-oxide (4NQO) solution with the concentration of 0.002% during the first 13 weeks, and then changed to normal water. The other 6 rats drank normal water all the time. During 25th to 30th week of the experiment, 2-Deoxy-2-[F-18]fluoro-D-glucose (FDG)-PET/CT was performed for these rats. One day after imaging, pathological examination was performed. SUVmax and T/NT were investigated according to pathological results. SAS6.0 software package was used for statistical analysis. RESULTS: There was no significant difference in SUVmax among the normal group, precancerous group and cancerous group (P>0.05). There was significant difference in T/NT (muscle, brain) between the normal group and the cancerous group (P 0.05); and no significant difference between the precancerous group and the cancerous group (P>0.05). The T/NT (muscle, brain) ratios increased along with the increase of the pathologic grade of the lesions. There was no significant difference in T/NT (thyroid) among the three groups and no correlation between the T/NT (thyroid) ratios and the pathologic grade. CONCLUSIONS: Micro PET/CT, as a non-invasive technology, may contribute to the dynamic studies of the process of carcinogenesis. T/NT (muscle, brain) ratios could show the degree of lesions of rat's tongue during carcinogenesis.%目的:研究Micro PET/CT在大鼠口腔黏膜癌前病变及口腔癌中的应用价值.方法:采用4NQO饮水法诱导大鼠舌癌模型,将39只大鼠随机分为实验组及空白对照组.实验25~30周,进行Micro PET/CT扫描.扫描后行组织病理学检查.应用SAS6.0软件包,对正常组、癌前病变组及癌变组大鼠的SUVmax、T/NT(肌肉)、T/NT(脑组织)及T/NT(甲状腺)分别进行方差分析,并对T/NT值和