PMID: 7513826May 1, 1994Paper

Chromosome aberrations: persistence of alkylation damage and modulation by O6-alkylguanine-DNA alkyltransferase

Mutation Research
C L BeanS M Galloway

Abstract

Alkylating agents produce a spectrum of DNA lesions alkylated at different sites on the molecule. These lesions differ in their propensities to cause effects such as cytotoxicity, mutations and sister-chromatid exchanges. We have used our observations that some methylating agents produce increasing levels of chromosome aberrations (abs) through successive cell cycles in Chinese hamster ovary cells, but not in normal human cells, to begin a study of which alkylated products are most likely to lead to chromosome abs, and in particular which adducts persist in DNA and cause abs after the first cell cycle. We previously observed increasing yields of abs with successive cell cycles in CHO-WBL cells treated with dimethyl nitrosamine (DMN), e.g., at 10 mM DMN, 8.8% cells with abs at first metaphase (M1) and 26.0% at third metaphase (M3) after treatment. Here we tested 4 methylating agents and their ethyl analogs in CHO cells, normal human fibroblasts (L136), and human lymphocytes. We sampled cells at several times after treating for 3 h (CHO and lymphocytes) or 4.5 h (L136). S9 metabolic activation was used for DMN and diethyl nitrosamine. BrdUrd labeling was used to identify cells in M1, M2 and M3. The methylating agents were more po...Continue Reading

References

Nov 1, 1990·Mutation Research
Jun 1, 1985·Mutation Research·K LarsonB Strauss
Jul 22, 1969·Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character·H J Evans, D Scott
Jul 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·A KatP Modrich

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Citations

Jan 1, 1994·Environmental and Molecular Mutagenesis·S M Galloway
Jun 1, 1994·Mutation Research·S M GallowayT Sofuni
Sep 5, 1998·Mutation Research·B Kaina
Jan 12, 2007·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Chih-Min LinTsing-Cheng Wang
Oct 22, 2009·Environmental and Molecular Mutagenesis·P Morales-RamírezV L Cruz-Vallejo
Sep 2, 2005·Mutagenesis·G J S JenkinsJ M Parry

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