The L5178Y/tk+/- mouse lymphoma specific gene and chromosomal mutation assay a phase III report of the U.S. Environmental Protection Agency Gene-Tox Program.
The L5178Y/tk+/- (-)3.7.2C mouse lymphoma assay (MLA) which detects mutations affecting the heterozygous thymidine kinase (tk) locus is capable of responding to chemicals acting as clastogens as well as point mutagens. Improvements in the assay to enhance detection of this spectrum of genetic events are summarized, and criteria for evaluating the data are defined. Using these criteria, the Phase III Work Group reviewed and evaluated literature containing MLA results published from 1976 through 1993. The data base included 602 chemicals of which 343 were evaluated as positive, 44 negative, 18 equivocal, 54 apparently inappropriate for evaluation in this test system with the published protocols, and 142 that were inadequately tested, and thus a definitive call could not be made. The overall performance of the assay is summarized by chemical class, and the outcome of testing 260 chemicals in the MLA is compared with Gene-Tox and National Toxicology Program evaluations of rodent carcinogenesis bioassay results for the same chemicals. Based on the Work Group's evaluation of published MLA data for chemicals that were considered adequately tested, it is concluded that for most chemicals the L5178Y/tk+/- mouse lymphoma assay is eminently well suited for genotoxicity testing and for predicting the potential for carcinogenicity.
Mitchell
A D
AD
Genesys Research, Incorporated, Research Triangle Park, NC 27709, USA.
Auletta
A E
AE
Clive
D
D
Kirby
P E
PE
Moore
M M
MM
Myhr
B C
BC
D000818:Animals; D002869:Chromosome Aberrations; D007940:Leukemia L5178 / Q000235:genetics*; D051379:Mice; D009154:Mutation; D012015:Reference Standards; D013937:Thymidine Kinase / Q000235:genetics*; D014407:Tumor Cells, Cultured; D014481:United States; D014484:United States Environmental Protection Agency
D013937:Thymidine Kinase