The mutagenic activity of selected compounds at the TK locus: rodent vs. human cells.
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.
Caspary
W J
WJ
Cellular and Genetic Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Langenbach
R
R
Penman
B W
BW
Crespi
C
C
Myhr
B C
BC
Mitchell
A D
AD
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
D009153:Mutagens; D013937:Thymidine Kinase