WorldWideScience

Sample records for cholanthrene

  1. Smoke carcinogens cause bone loss through the aryl hydrocarbon receptor and induction of CYP1 enzymes

    Science.gov (United States)

    Smoking is a major risk factor for osteoporosis and fracture. Here, we show that smoke toxins and environmental chemicals such as benzo[a]pyrene (BaP), 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD), and 3-methyl cholanthrene, which are well known aryl hydrocarbon receptor (AHR) agonists, induce osteocla...

  2. Phytoplankton growth, dissipation, and succession in estuarine environments. Renewal proposal and annual summary report, August 1, 1977--July 31, 1978

    Energy Technology Data Exchange (ETDEWEB)

    Seliger, H H

    1978-01-01

    The directions of the research program in understanding the dynamics of the natural phytoplankton populations of the Chesapeake Bay, the methodology, the statistical analysis, and the description of the system are parallel to the requirements for environmental impact studies. Results are reported for the following studies: development of instrumentation and the synoptic isopleth methodology for relating the dynamic distributions of natural phytoplankton populations to water circulation patterns; phytoplankton cage experiments for assessment of nutrient dynamics; sub-lethal concentrations and effects of polycyclic aromatic hydrocarbons; and studies on concentration and time kinetics of induction of liver aryl hydrocarbon hydroxylase system in Fundulus heteroclitus by benzopyrene and 3-methyl cholanthrene. (HLW)

  3. Aflatoxin B1 metabolism by 3-methylcholanthrene-induced hamster hepatic cytochrome P-450s.

    Science.gov (United States)

    Lai, T S; Chiang, J Y

    1990-01-01

    We have studied the activation of aflatoxin B1 by hamster liver microsomes and purified hamster cytochrome P-450 isozymes using a umu mutagen test. The hamster liver microsomes or S-9 fractions were much more active than rat liver microsomes or S-9 fractions in the activation of umu gene expression by aflatoxin B1 metabolites. 3-Methyl-cholanthrene treatment increased aflatoxin B1 activation by hamster liver microsomes. Two major 3-methylcholanthrene-inducible cytochrome P-450 isozymes, P-450 MC1 (IIA) and P-450 MC4 (IA2), were purified from 3-methylcholanthrene-treated hamster liver microsomes, and the metabolism of aflatoxin B1 by these two cytochromes was studied. In the reconstituted enzyme system, both P-450 MC1 and P-450 MC4 were highly active in the activation of aflatoxin B1, and antibodies against these P-450s specifically inhibited these activities. Antibody against P-450 MC1 inhibited the activation of aflatoxin B1 by 20% in the presence of 3-methyl-cholanthrene-treated hamster liver microsomes. In contrast, antibody against P-450 MC4 stimulated the activity by 175%. These results indicated that hamster P-450 MC1 might convert aflatoxin B1 to more toxic metabolite(s), whereas P-450 MC4 might convert aflatoxin B1 to less toxic metabolite(s), than aflatoxin B1 in liver microsomes. The metabolite(s) produced by both hamster cytochrome P-450 MC1 and MC4 were genotoxic in the umu mutagen test. PMID:2126562

  4. Safrole-DNA adducts in tissues from esophageal cancer patients: clues to areca-related esophageal carcinogenesis.

    Science.gov (United States)

    Lee, Jang-Ming; Liu, Tsung-Yung; Wu, Deng-Chyang; Tang, Hseau-Chung; Leh, Julie; Wu, Ming-Tsang; Hsu, Hsao-Hsun; Huang, Pei-Ming; Chen, Jin-Shing; Lee, Chun-Jean; Lee, Yung-Chie

    2005-01-01

    Epidemiological studies have demonstrated that areca quid chewing can be an independent risk factor for developing esophageal cancer. However, no studies are available to elucidate the mechanisms of how areca induces carcinogenesis in the esophagus. Since the areca nut in Taiwan contains a high concentration of safrole, a well-known carcinogenic agent, we analyzed safrole-DNA adducts by the 32P-postlabelling method in tissue specimens from esophageal cancer patients. In total, we evaluated 47 patients with esophageal cancer (16 areca chewers and 31 non-chewers) who underwent esophagectomy at the National Taiwan University Hospital between 1996 and 2002. Of the individuals with a history of habitual areca chewing (14 cigarette smokers and two non-smokers), one of the tumor tissue samples and five of the normal esophageal mucosa samples were positive for safrole-DNA adducts. All patients positive for safrole-DNA adducts were also cigarette smokers. Such adducts could not be found in patients who did not chew areca, irrespective of their habits of alcohol consumption or cigarette smoking (psafrole was also tested in vitro in three esophageal cell lines and four cultures of primary esophageal keratinocytes. In two of the esophageal keratinocyte cultures, adduct formation was increased by treatment with safrole after induction of cytochrome P450 by 3-methyl-cholanthrene. This paper provides the first observation of how areca induces esophageal carcinogenesis, i.e., through the genotoxicity of safrole, a component of the areca juice.

  5. Role of lipid peroxidation in cytochrome P-450 degradation in hepatocytes and lymphocytes and stabilizing effects of antioxidants

    Energy Technology Data Exchange (ETDEWEB)

    Kagan, V.; Novikov, K.; Bogdanova, E.; Prilipko, L.

    1986-01-01

    Incubation of primary culture of hepatocytes was accompanied by spontaneous degradation of cytochrome P-450 (P-450) and by a decrease of its monooxygenase activities. Accumulation of lipid peroxidation (LPO) products also occurred. Addition of LPO inducers (Fe/sup 2 +/-ADP, NADPH) to the medium led to a drastic acceleration of both processes. Synthetic free radical scavengers (butylated hydroxytoluene, 3-hydroxybenzene, alpha-naphthol) prevented LPO activation and protected P-450 against degradation. Phenolic derivatives of 3,4-benzpyrene, formed as a result of its hydroxylation, also had an antioxidant and a protective effect on P-450. Similarly, incubation of human peripheral blood lymphocytes stimulated by PHA resulted in a rapid inhibition of arylhydrocarbon hydroxylase (AHH). In lymphocytes stimulated by PHA and then induced by 3-methylcholanthrene, the sharply increased AHH activity remained unchanged for a long period and no LPO products were accumulated. Exogenous LPO inducers did not either stimulate LPO and were ineffective on the AHH activity. This was due to the presence of 3-methyl cholanthrene phenolic derivatives formed during lymphocytes induction. It is concluded that free radical scavengers could be used as P-450 stabilizers in cell cultures.

  6. 4-nitroquinoline-1-oxide induced experimental oral carcinogenesis.

    Science.gov (United States)

    Kanojia, Deepak; Vaidya, Milind M

    2006-08-01

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