title: The mutagenic activity of selected compounds at the TK locus: rodent vs. human cells.
abstract: The mutagenic (TFT resistance) and toxic responses of mouse lymphoma (MOLY) L5178Y cells and human lymphoblast (HULY) TK6 cells were compared for 13 chemicals. The mutagenic activities of 8 of the 13 chemicals (62%) examined in the HULY and MOLY assays are in agreement - the results being judged positive in both assays. However, a dramatic difference is observed when the two conditions of metabolic activation are considered separately; the overall concordance of 8/13 has been achieved by combining a 13/13 (100%) agreement in the absence of S9 with a 1/6 (17%) agreement in the presence of S9. In the absence of S9, the concentration ranges, lowest significant doses, and shapes of the concentration-response curves for both toxicity and mutagenicity were similar in spite of the differences in exposure times (4 h for MOLY, 20 for HULY) and expression times (2 days for MOLY, 3 days for HULY). The general agreement observed in the absence of S9 contrasted with the differences manifested in its presence. 6 compounds which were negative in the absence of S9 were tested in both the MOLY and HULY assays in the presence of S9. Of the 6 chemicals, only 1 was positive in both MOLY and HULY under the latter condition; 4 others were positive in MOLY and negative in HULY whereas 1 was positive in HULY and negative in MOLY.
authors.affiliation: Cellular and Genetic Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
authors.forename: W J
authors.initials: WJ
authors.lastname: Caspary
authors.forename: R
authors.initials: R
authors.lastname: Langenbach
authors.forename: B W
authors.initials: BW
authors.lastname: Penman
authors.forename: C
authors.initials: C
authors.lastname: Crespi
authors.forename: B C
authors.initials: BC
authors.lastname: Myhr
authors.forename: A D
authors.initials: AD
authors.lastname: Mitchell
mesh_terms: D000818:Animals; D001711:Biotransformation; D002470:Cell Survival; D005796:Genes / Q000187:drug effects; D006801:Humans; D007940:Leukemia L5178 / Q000235:genetics; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens; D013045:Species Specificity; D013937:Thymidine Kinase / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D009153:Mutagens; D013937:Thymidine Kinase