PMID: 20650122Aug 1, 1995Paper

Molecular analysis of chemically-induced mutations in mammalian cell assays

Toxicology in Vitro : an International Journal Published in Association with BIBRA
M J DaviesP C Rumsby

Abstract

Two mammalian cell mutation assays, the HPRT/V79 assay and the TK/mouse lymphoma assay, were compared for their ability to respond to the genotoxic chemicals ethyl methanesulfonate (EMS) and mitomycin C (MMC). Whereas EMS induced a high mutant frequency at both loci, MMC produced few mutants at the hprt locus, but induced a large number of mutants at the tk locus. Southern blotting analysis showed that this difference was due to the type of genetic damage induced by the two chemicals. Intragenic changes ranging from point mutations to loss of the entire gene were recovered as viable mutants at both the hprt and tk loci. Thus, EMS which causes mainly intragenic mutations induced similar mutant frequencies at both loci. The large multilocus deletions induced by MMC, in which the damage was assumed in many cases to extend into a gene essential for growth since most TK mutants were slow-growing, could not be recovered at the hprt locus. Whereas both loci will detect intergenic mutations, mutants carrying large-scale damage are recoverable only at the heterozygous tk locus. At the hemizygous hprt locus no homologous chromosome exists to provide the function of essential genes if these are lost along with hprt in multilocus deletions...Continue Reading

References

Jan 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·M L ApplegateJ C Hozier
Jun 1, 1983·Mutation Research·D CliveK H Mavournin

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Citations

Jan 18, 2016·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·David KirklandRaffaella Corvi

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