Metabolic activation of chemicals to mutagenic carcinogens by human hepatoma microsomal extracts in Chinese hamster ovary cells (in vitro).
The efficiency of human hepatoma (Hep G2) S9 microsomal fractions to activate indirectly acting genotoxic carcinogens was evaluated. The extract was prepared from Hep G2 epithelial cells, following sonication and centrifugation. The mutagenic activity of cyclophosphamide, benzo[a]pyrene, pyrene, hexamethylphosphoramide and safrole was assessed by the ability of their activated metabolites to induce sister chromatid exchange (SCE) and micronuclei (MN) in Chinese hamster ovary cells (CHO) (treated in vitro). All promutagenic carcinogens tested were found to be effective only following metabolic activation by Hep G2 cell extracts. Non-carcinogen pyrene was not able to induce an increase in the frequencies of SCE or MN in CHO cells even in the presence of Hep G2 S9 microsomal fractions. Parallel experiments were carried out using rat liver homogenate (S9 fraction) as an exogenous activation system, and comparisons were made between these two in vitro systems and in vivo assays using the rodent.
Darroudi
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Department of Radiation Genetics and Chemical Mutagenesis, State University of Leiden, Sylvius Laboratories, The Netherlands.
Natarajan
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D000818:Animals; D001711:Biotransformation; D016466:CHO Cells / Q000187:drug effects*; D002273:Carcinogens / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology; D002457:Cell Extracts; D006224:Cricetinae; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology; D008862:Microsomes, Liver / Q000378:metabolism*; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D051381:Rats
D002273:Carcinogens; D002457:Cell Extracts; D009153:Mutagens; D009363:Neoplasm Proteins