Mutagenic evaluation of carcinogens and non-carcinogens in the L5178Y/TK assay utilizing postmitochondrial fractions (S9) from normal rat liver.

As part of continuing effort to investigate various metabolic activation procedures in the L5178Y TK +/- leads to TK -/- mutation assay, a series of 18 chemicals including both carcinogens and non-carcinogens selected from 7 chemical classes were tested in the presence of 5% (v/v) 9000 x g postmitochondrial supernatant fraction (S9) prepared from the livers of untreated Sprague-Dawley rats. Excepting ethyl carbamate and thioacetamide, 8 of 10 carcinogens tested produced mutant counts significantly greater than controls when the results were analyzed by a 2-sample loge t-test. Of 8 non-carcinogens assayed, treatment with p-aminophenol and chloroacetic acid yielded mutant counts significantly greater than control levels in at least one test with S9 while styrene oxide, an Ames positive mutagen, produced mutagenic activity in the absence of S9. These results indicate the L5178Y TK +/- leads to TK -/- mutation assay coupled with 5% (v/v) liver homogenate from normal rodent liver and applied to 18 chemicals correctly distinguished the majority of carcinogens from structurally related non-carcinogens on the basis of chemically-induced gene mutations.