Mutagenicity testing with the Salmonella/hepatocyte and the Salmonella/microsome assays. A comparative study with some known genotoxic compounds.
The applicability of isolated intact hepatocytes as a metabolic factor in bacterial mutagenicity screening was studied. Mutagenic activities of 12 known premutagenic compounds were determined in a Salmonella typhimurium test system comprising hepatocytes and were compared with mutagenicity data obtained with the commonly used Salmonella/microsome plate assay. In a qualitative sense the results obtained with the two systems were, in general, equivalent. However, some specific differences were found depending on the bacterial strain used. For instance, dimethylnitrosamine was only mutagenic for Salmonella strain TA1535 in the hepatocyte suspension system. On the other hand, benzo[a]pyrene was hardly mutagenic towards TA100 with hepatocytes in contrast with the clear-cut effects in the microsome plate assay. In a quantitative respect, for benzidine, 2-acetylaminofluorene, 2-aminoanthracene and dimethylnitrosamine, obviously divergent mutagenic values were recorded with the different procedures. These differences were found to be connected with the presence of intact hepatocytes. This appeared from a comparison between mutagenicities with intact hepatocytes and with S9 prepared from disrupted hepatocytes. The results support previous recommendations that tests with intact cell metabolism should be included in a battery for screening of carcinogens in vitro.
D000818:Animals; D001711:Biotransformation; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens; D009154:Mutation / Q000187:drug effects; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects*; D013997:Time Factors
D009153:Mutagens