Evaluation of the L5178Y mouse lymphoma cell mutagenesis assay: interlaboratory reproducibility and assessment.
The L5178Y mouse lymphoma cell mutagenesis assay is used to detect the mutagenic activity of chemicals in a mammalian cell system. To evaluate this assay we compared the results of assays performed independently on 63 chemicals by laboratories at SRI International and Litton Bionetics, Inc. The two laboratories used similar protocols. The solvent and positive control mutant frequencies and cloning efficiencies obtained by the two laboratories were similar, which justified the use of the same quality-control criteria and analytical procedures for analyzing the results from both laboratories. The rate of concordance between the two laboratories was 92% for tests in the absence of S9 activation and 95% for tests in its presence. The results of the assays agreed for 57 of the 63 chemicals; three chemicals could not be compared because there were questionable calls in at least one of the laboratories; the results disagreed for the three remaining chemicals. The concordance rate for these overall assay evaluations was 95%. The interlaboratory concordance rates were similar to concordance rates for replicate experiments within the laboratories (96% at LBI, 94% at SRI). The mouse lymphoma cell mutagenicity results are concordant with the rodent chronic assay results in 78% of 50 chemicals and with the Salmonella assay results in 79% of 56 chemicals. Fifteen carcinogens were examined for genotoxic effects in mouse lymphoma, Salmonella, Chinese hamster ovary (CHO) chromosomal aberration, and CHO sister chromatid exchange assay. Eight of these were positive in all four assays. Of the seven noncarcinogens that were tested in these four assays, none was negative in all four. The main conclusion to be drawn from this study is that the mouse lymphoma cell forward mutation assay, as performed and evaluated in this study, detects chemical mutagenicity in a manner that is highly consistent with other genetic endpoints as well as rodent carcinogenicity studies. Thus the assay quality control and response criteria established in this study led not only to a high degree of reproducibility but also to an apparently reliable detection of mutagenic activity.
Caspary
W J
WJ
Cellular and Genetic Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina.
Daston
D S
DS
Myhr
B C
BC
Mitchell
A D
AD
Rudd
C J
CJ
Lee
P S
PS
D000818:Animals; D002452:Cell Count; D011232:Chemical Precipitation; D002999:Clone Cells; D004305:Dose-Response Relationship, Drug; D005069:Evaluation Studies as Topic; D007940:Leukemia L5178; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D011237:Predictive Value of Tests; D011786:Quality Control; D014407:Tumor Cells, Cultured
D009153:Mutagens