THE L5178Y TK(+/-) MOUSE LYMPHOMA SPECIFIC GENE AND CHROMOSOMAL MUTATION ASSAY - A PHASE-III REPORT OF THE US ENVIRONMENTAL-PROTECTION-AGENCY GENE-TOX PROGRAM/

The L5178Y/tk(+/-)-3.7.2C mouse lymphoma assay (MLA) which detects mut ations affecting the heterozygous thymidine kinase (rk) locus is capab le of responding to chemicals acting as clastogens as well as point mu tagens. Improvements in the assay to enhance detection of this spectru m of genetic events are summarized, and criteria for evaluating the da ta are defined. Using these criteria, the Phase III Work Group reviewe d and evaluated literature containing MLA results published from 1976 through 1993. The data base included 602 chemicals of which 343 were e valuated as positive, 44 negative, 18 equivocal, 54 apparently inappro priate for evaluation in this test system with the published protocols , and 142 that were inadequately tested, and thus a definitive call co uld not be made. The overall performance of the assay is summarized by chemical class, and the outcome of testing 260 chemicals in the MLA i s compared with Gene-Tox and National Toxicology Program evaluations o f rodent carcinogenesis bioassay results for the same chemicals. Based on the Work Group's evaluation of published MLA data for chemicals th at were considered adequately tested, it is concluded that for most ch emicals the L5178Y/tk(+/-) mouse lymphoma assay is eminently well suit ed for genotoxicity testing and for predicting the potential for carci nogenicity. (C) 1997 Elsevier Science B.V.