Comparison of the metabolic activation of 7, 12-dimethylbenz(a)anthracene by a human hepatoma cell line (HepG2) and low passage hamster embryo cells.
Under similar conditions of cell-mediated mutagenesis, secondary hamster embryo (HE) cells were much more effective than were cells of the human hepatoma cell line, HepG2 , in activating 7, 12-dimethylbenz(a)anthracene (DMBA) to metabolites mutagenic for V79 Chinese hamster cells. At the same dose of DMBA (0.1 microgram/ml), mutation induction (6-thioguanine resistance) with HE cells as activators was about ten times greater than with HepG2 cells as activators. Both cell types rapidly metabolized DMBA. HepG2 cells converted DMBA primarily to water-soluble derivatives that were neither sulfates nor glucuronides, whereas HE cells converted DMBA to a variety of organic solvent-soluble and water-soluble metabolites. The major water-soluble metabolites produced by HE cells were phenol-glucuronides. In HepG2 cells, binding of DMBA to DNA reached a maximum value of 12.1 pmol/mg DNA at 12 hr, whereas in HE cells, binding reached a peak value of 180.7 pmol/mg DNA at 24 hr. Despite this difference in total binding between the two cell types, the pattern of DNA adducts formed was nearly identical. The results indicate that the marked difference in the ability of HepG2 and HE cells to activate DMBA in cell-mediated mutation assays is not due to a lower metabolizing capacity of HepG2 cells for DMBA. Rather, significant differences in the metabolic pathways used by the two cell types lead to a marked reduction in DNA-binding metabolites in one cell type ( HepG2 ) compared to the other (HE).
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D001711:Biotransformation; D002250:Carbon Radioisotopes; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D002999:Clone Cells; D006224:Cricetinae; D003412:Cricetulus; D004622:Embryo, Mammalian; D006801:Humans; D007700:Kinetics; D008113:Liver Neoplasms / Q000378:metabolism*; D008168:Lung; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation
D001551:Benz(a)Anthracenes; D002250:Carbon Radioisotopes; D009153:Mutagens; D015127:9,10-Dimethyl-1,2-benzanthracene