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The L5178Y/tk+/- mouse lymphoma specific gene and chromosomal mutation assay a phase III report of the U.S.
A D Mitchell1, A E Auletta, D Clive
1Genesys Research, Incorporated, Research Triangle Park, NC 27709, USA.
Abstract:
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.
Insights
The mouse lymphoma assay (MLA) effectively detects genetic mutations caused by various chemicals. This genotoxicity test is well-suited for predicting potential carcinogenicity in chemicals.
Area of Science:
- Toxicology
- Genetics
- Molecular Biology
Background:
- The L5178Y/tk+/- mouse lymphoma assay (MLA) detects mutations at the thymidine kinase (tk) locus.
- This assay responds to both clastogens and point mutagens, indicating its broad applicability in genotoxicity testing.
Purpose of the Study:
- To summarize improvements in the MLA for enhanced detection of genetic events.
- To define criteria for evaluating MLA data.
- To assess the overall performance and predictive value of the MLA for carcinogenicity.
Main Methods:
- A Phase III Work Group reviewed and evaluated published MLA results from 1976-1993.
- Data from 602 chemicals were analyzed, categorizing them as positive, negative, equivocal, inappropriate, or inadequately tested.
- MLA results for 260 chemicals were compared with Gene-Tox and National Toxicology Program rodent carcinogenicity bioassay data.
Main Results:
- Out of 602 chemicals, 343 were positive, 44 negative, 18 equivocal, 54 inappropriate, and 142 inadequately tested.
- The assay's performance was summarized by chemical class.
- A strong correlation was observed between MLA results and rodent carcinogenicity bioassays for adequately tested chemicals.
Conclusions:
- The L5178Y/tk+/- mouse lymphoma assay is highly suitable for genotoxicity testing.
- The MLA demonstrates significant utility in predicting the carcinogenic potential of chemicals.
- Established criteria enhance the reliability and interpretability of MLA data.
