An evaluation of the L5178Y TK+/- mouse lymphoma forward mutation assay using 42 chemicals

The L5178YTK+/- mouse lymphoma assay (MLA) has been utilized in several laboratories as a short-term test for chemical-induced forward mutation in cultured mammalian cells. In order to evaluate several technical modifications to the MLA, 42 chemicals representing 9 chemical classes were tested and the results were compared with those published elsewhere as well as with findings in a genetic toxicology test battery currently used in this laboratory. A positive response for the induction of TK-/- mutants was obtained for 26 chemicals. With the exception of p-aminophenol, all of these compounds were recognized mutagens or carcinogens and were representative of direct-acting and activation-dependent genotoxins. 16 compounds did not induce TK-/- mutants and among these were 5 compounds that were considered to be mutagens or carcinogens. A comparison of the results of this study with those published elsewhere revealed a strong agreement among findings for this test irrespective of minor technical variations. It was concluded that the MLA is a useful system for identifying chemical mutagens in mammalian cells and can serve as a valuable component in a genetic toxicology test battery.