Sister-chromatid exchange induction by indirect mutagens/carcinogens, aryl hydrocarbon hydroxylase activity and benzo[alpha]pyrene metabolism in cultured human hepatoma cells. 1983

S Abe, and N Nemoto, and M Sasaki

2 human hepatoma cell lines (C-HC-4 and C-HC-20), in which aryl hydrocarbon hydroxylase activity was induced with benz[alpha]anthracene in vitro to about 140- and 64-fold of the respective basal levels, yielded an increased frequency of sister-chromatid exchanges (SCEs) when exposed to benzo[alpha]pyrene (BP), 7,12-dimethylbenz[alpha]anthracene and 3-methylcholanthrene in vitro. Analysis of the metabolism of BP by these cells by high-pressure liquid chromatography revealed that both cell lines produced various BP metabolites including the proximate form BP-7,8-dihydrodiol which has been reported to be the most potent inducer of SCEs among the metabolites of BP. In addition, aflatoxin B1 and cyclophosphamide also induced SCEs in these cell lines. The above findings suggest that these cells may be capable of metabolizing a range of indirect mutagens/carcinogens into DNA-active forms. These cells may therefore serve as a useful test system in vitro for the detection of genotoxic agents, without the use of an exogenous activating system.

UI MeSH Term Description Entries
D008113 Liver Neoplasms Tumors or cancer of the LIVER. Cancer of Liver,Hepatic Cancer,Liver Cancer,Cancer of the Liver,Cancer, Hepatocellular,Hepatic Neoplasms,Hepatocellular Cancer,Neoplasms, Hepatic,Neoplasms, Liver,Cancer, Hepatic,Cancer, Liver,Cancers, Hepatic,Cancers, Hepatocellular,Cancers, Liver,Hepatic Cancers,Hepatic Neoplasm,Hepatocellular Cancers,Liver Cancers,Liver Neoplasm,Neoplasm, Hepatic,Neoplasm, Liver
D009152 Mutagenicity Tests Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests. Genetic Toxicity Tests,Genotoxicity Tests,Mutagen Screening,Tests, Genetic Toxicity,Toxicity Tests, Genetic,Genetic Toxicity Test,Genotoxicity Test,Mutagen Screenings,Mutagenicity Test,Screening, Mutagen,Screenings, Mutagen,Test, Genotoxicity,Tests, Genotoxicity,Toxicity Test, Genetic
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D003434 Crossing Over, Genetic The reciprocal exchange of segments at corresponding positions along pairs of homologous CHROMOSOMES by symmetrical breakage and crosswise rejoining forming cross-over sites (HOLLIDAY JUNCTIONS) that are resolved during CHROMOSOME SEGREGATION. Crossing-over typically occurs during MEIOSIS but it may also occur in the absence of meiosis, for example, with bacterial chromosomes, organelle chromosomes, or somatic cell nuclear chromosomes. Crossing Over,Crossing-Over, Genetic,Crossing Overs,Genetic Crossing Over,Genetic Crossing-Over
D003520 Cyclophosphamide Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. (+,-)-2-(bis(2-Chloroethyl)amino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-Oxide Monohydrate,B-518,Cyclophosphamide Anhydrous,Cyclophosphamide Monohydrate,Cyclophosphamide, (R)-Isomer,Cyclophosphamide, (S)-Isomer,Cyclophosphane,Cytophosphan,Cytophosphane,Cytoxan,Endoxan,NSC-26271,Neosar,Procytox,Sendoxan,B 518,B518,NSC 26271,NSC26271
D004790 Enzyme Induction An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis. Induction, Enzyme
D006528 Carcinoma, Hepatocellular A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested. Hepatocellular Carcinoma,Hepatoma,Liver Cancer, Adult,Liver Cell Carcinoma,Liver Cell Carcinoma, Adult,Adult Liver Cancer,Adult Liver Cancers,Cancer, Adult Liver,Cancers, Adult Liver,Carcinoma, Liver Cell,Carcinomas, Hepatocellular,Carcinomas, Liver Cell,Cell Carcinoma, Liver,Cell Carcinomas, Liver,Hepatocellular Carcinomas,Hepatomas,Liver Cancers, Adult,Liver Cell Carcinomas
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000348 Aflatoxins Furano-furano-benzopyrans that are produced by ASPERGILLUS from STERIGMATOCYSTIN. They are structurally related to COUMARINS and easily oxidized to an epoxide form to become ALKYLATING AGENTS. Members of the group include AFLATOXIN B1; aflatoxin B2, aflatoxin G1, aflatoxin G2; AFLATOXIN M1; and aflatoxin M2. Aflatoxin
D001189 Aryl Hydrocarbon Hydroxylases A large group of cytochrome P-450 (heme-thiolate) monooxygenases that complex with NAD(P)H-FLAVIN OXIDOREDUCTASE in numerous mixed-function oxidations of aromatic compounds. They catalyze hydroxylation of a broad spectrum of substrates and are important in the metabolism of steroids, drugs, and toxins such as PHENOBARBITAL, carcinogens, and insecticides. Microsomal Monooxygenases,Xenobiotic Monooxygenases,Hydroxylases, Aryl Hydrocarbon,Monooxygenases, Microsomal,Monooxygenases, Xenobiotic

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