PMID: 9639696Jun 26, 1998Paper

Comparative mutational spectra of the nitrogen mustard chlorambucil and its half-mustard analogue in Chinese hamster AS52 cells

Mutation Research
B M YaghiL R Ferguson

Abstract

Nitrogen mustards play an important role in current cancer chemotherapy. The most effective antitumour agents are those carrying two alkylating functions, probably through their ability to form interstrand cross-links in DNA. Such lesions appear to create more of a block in DNA replication and are more difficult to repair than are most monoadducts. Although there were early reports that monofunctional drugs were more mutagenic than the bifunctional drugs, this has not been formally proved using structurally related drugs in a mutagenicity assay capable of detecting a range of different events. We have studied both the mutagenic potency and spectrum of events caused by treatment with the clinical agent, chlorambucil, compared with its half-mustard analogue, in Chinese hamster ovary (CHO)-AS52 cells. Although both drugs caused comparable increases in mutation frequency at doses killing 90% of cells (from around 9x10-6 to around 9x10-5 mutant cells), the nature of events differed significantly between the drugs. By far the majority of mutations caused by the half-mustard were transversion mutations, and almost all of these could be interpreted in relation to the DNA adducts that are known to be formed. In contrast, the majority of...Continue Reading

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Citations

Apr 28, 2004·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·Nazreen MalikFrank Brady
Feb 9, 2006·Chemical Reviews·David M NollPaul S Miller
Sep 2, 2005·Mutagenesis·G J S JenkinsJ M Parry
Sep 3, 2010·Critical Reviews in Biochemistry and Molecular Biology·Lily C Wang, Jean Gautier
Jul 23, 2009·Chemical Research in Toxicology·Dalia MohamedMichael W Linscheid

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