The use of L5178Y mouse lymphoma cells to assess the mutagenic, clastogenic and aneugenic properties of chemicals.
Guidelines have been proposed to assess the potential of chemicals to affect human health. Written into these guidelines is the requirement that information be submitted on mutagenic activity. Although regulatory agencies accept mutagenicity data from both the hprt and tk loci in mammalian cells, many studies suggest that the L5178Y mouse lymphoma assay at the thymidine kinase locus is likely to detect a greater spectrum of mutagenic lesions. Thus, there is increasing emphasis being placed on this assay in many proposed and published guidelines. The L5178Y mouse lymphoma suspension protocol produces both small and large colonies which are the products of mutants growing at different rates. There is a reduction in the proportion of slowly growing mutants with respect to the total population of cells when expression is carried out in suspension. This potentially leads to quantitatively inaccurate assessments of the mutagenic activity of chemicals. Therefore an in situ procedure was developed that more accurately assesses the mutagenic activity of chemicals by maximizing the detection of small colonies. Many guidelines recommend tests that assess the clastogenic activity of chemicals. Some regulatory agencies accept data from the mouse lymphoma mutation assay to detect clastogens if the protocol is optimized for the detection of small colonies or if colony sizing data are submitted. The conventional suspension assay protocol is not sufficiently validated for this purpose. The in situ protocol has greater potential to meet these requirements.(ABSTRACT TRUNCATED AT 250 WORDS)
Combes
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RD
Fund for the Replacement of Animals in Medical Experiments (FRAME), Nottingham, UK.
Stopper
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Caspary
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WJ
D000782:Aneuploidy; D000818:Animals; D002452:Cell Count; D048429:Cell Size; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000187:drug effects; D004351:Drug Resistance; D017408:Guidelines as Topic; D007940:Leukemia L5178 / Q000473:pathology*; D051379:Mice; D015162:Micronucleus Tests / Q000592:standards; D009152:Mutagenicity Tests / Q000592:standards*; D009154:Mutation; D013937:Thymidine Kinase / Q000235:genetics; D014271:Trifluridine / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D014410:Tumor Stem Cell Assay / Q000592:standards; D014481:United States; D014486:United States Food and Drug Administration
D013937:Thymidine Kinase; D014271:Trifluridine