Use of human hepatoma cells for in vitro metabolic activation of chemical mutagens/carcinogens.
An established human hepatoma cell strain (Hep G2) was used in micronuclei (MN) and sister chromatid exchange (SCE) assays to evaluate the clastogenic potential of several indirectly-acting mutagenic carcinogens. Benzo[a]pyrene, cyclophosphamide, dimethyl nitrosamine, hexamethylphosphoramide, pyrene and safrole were selected for this study based on the positive and negative results reported with conventional in vitro assays employing rat liver S9 fraction for metabolic activation. Two directly-acting mutagens, methyl methanesulphonate and mitomycin C, were also included in this study. In this system, the human hepatoma cells act as the metabolic activation source as well as the target cell for DNA damage. The results obtained demonstrate that the Hep G2 cells are metabolically competent to activate different classes of mutagens into biologically active metabolites. The non-carcinogen pyrene did not induce any increase in the frequencies of MN and SCE in Hep G2 cells. Furthermore, a good correlation was found between positive and negative data obtained for the tested chemicals in this in vitro assay with literature data obtained in in vivo tests using rodents.
Natarajan
A T
AT
MGC, Department of Radiation Genetics and Chemical Mutagenesis, State University of Leiden, Sylvius Laboratories, The Netherlands.
Darroudi
F
F
D001711:Biotransformation; D015197:Carcinogenicity Tests / Q000379:methods*; D002273:Carcinogens / Q000493:pharmacokinetics* / Q000633:toxicity; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism; D015162:Micronucleus Tests; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000493:pharmacokinetics* / Q000633:toxicity; D012854:Sister Chromatid Exchange; D014407:Tumor Cells, Cultured / Q000378:metabolism*
D002273:Carcinogens; D009153:Mutagens