Chemical mutagenesis at the thymidine kinase locus in L5178Y mouse lymphoma cells: Results for 31 coded compounds in the national toxicology program

• Published in: Environmental and molecular mutagenesis 1991, Vol.18 (1), p.51-83
• Main Authors: Myhr, Brian C., Caspary, William J., Holden, H. E.
• Format: Article
• Language: English
• Subjects: 560300 - Chemicals Metabolism & Toxicology; ACETATES; ANIMAL CELLS; ANIMALS; AROMATICS; ASCORBIC ACID; Biological and medical sciences; Biotransformation; BROMINATED AROMATIC HYDROCARBONS; CARBOXYLIC ACID SALTS; CARCINOGENS; CHALCOGENIDES; Chemical mutagenesis; CHLORIDES; CHLORINATED AROMATIC HYDROCARBONS; CHLORINE COMPOUNDS; COORDINATED RESEARCH PROGRAMS; DISEASES; ELEMENTS; genotoxicity; HALIDES; HALOGEN COMPOUNDS; HALOGENATED AROMATIC HYDROCARBONS; IMMUNE SYSTEM DISEASES; Leukemia L5178 - enzymology; Leukemia L5178 - genetics; LYMPHOMAS; Male; MAMMALS; Medical sciences; METALS; MICE; Microsomes, Liver - metabolism; MUTAGEN SCREENING; MUTAGENESIS; Mutagenicity Tests - methods; Mutagens - pharmacology; National Institutes of Health (U.S.); NEOPLASMS; ORGANIC BROMINE COMPOUNDS; ORGANIC CHLORINE COMPOUNDS; ORGANIC COMPOUNDS; ORGANIC HALOGEN COMPOUNDS; PHTHALATES; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT; RATS; Rats, Inbred F344; Research Design; RESEARCH PROGRAMS; RODENTS; SCREENING; SELENIUM COMPOUNDS; SELENIUM SULFIDES; SULFIDES; SULFUR COMPOUNDS; Thymidine Kinase - genetics; TIN CHLORIDES; TIN COMPOUNDS; TIN HALIDES; TITANIUM; TK locus; Toxicology; TRANSITION ELEMENTS; trifluorothymidine resistance; TUMOR CELLS; United States; VERTEBRATES; VITAMINS
• ISSN: 0893-6692; 0364-152X; 1098-2280; 1432-1009
• DOI: 10.1002/em.2850180109

Experimental data from the testing of 31 chemicals for mutagenicity at the TK locus in L5178Y mouse lymphoma cells are presented and evaluated. If mutagenic activity was not obtained for the chemical added to suspension cultures for 4 hr, then the testing was repeated in the presence of hepatic S9 mix prepared from Aroclor 1254‐induced male Fischer 344 rats. Multiple trials were performed for each chemical, and mutagenic treatments were analyzed for the induction of small and large mutant colony populations. Twelve chemicals were not detected as mutagenic, one (ascorbic acid) was questionable, and 18 were evaluated as mutagenic. These results were used in the evaluations presented by Tennant et al. [Science 236:933–941, 1987] in a critical comparison of four in vitro genotoxicity assays with rodent carcinogenicity results. The mouse lymphoma assay results were in general agreement with the carcinogenicity studies. Discordant evaluations with respect to carcinogenicity (four false negatives and six false positives) were discussed from the standpoint of how the predictive performance of the in vitro mutation assay might be improved.