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Mutagenesis Advance Access published online on April 30, 2009
Mutagenesis, doi:10.1093/mutage/gep012
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© The Author 2009. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Enhancement of the recombinagenic and mutagenic activities of bleomycin in yeast by intercalation of acridine compounds into DNA

George R. Hoffmann*, Matthew V. Ronan, Katelyn E. Sylvia and Jason P. Tartaglione

Department of Biology, College of the Holy Cross, One College Street, Worcester, MA 01610-2395, USA

Strain D7 of Saccharomyces cerevisiae was used to measure the induction by bleomycin (BLM) of mitotic recombination at the trp5 locus and point mutations at ilv1 in the presence and absence of acridine compounds. BLM is a potent mutagen and recombinagen in the D7 assay. The acridines vary, some being mutagenic or recombinagenic and others not. Combined treatments were used to distinguish whether a genetically inactive acridine has no effect on the genetic activity of BLM or modulates its action. When an acridine is itself genetically active, combined treatments were used to determine whether its effects are additive with those of BLM or whether there is interaction between the two compounds. Acridine compounds that share the ability to intercalate between the base pairs of DNA but differ in their mutagenic specificity owing to the presence of different substituent groups were analysed. Clear potentiation and synergistic interactions were detected in combined treatments with BLM and aminoacridines, nitroacridines or an acridine mustard. Potentiation and synergy were also observed in sequential exposures in which the yeast were grown in the presence of acridine compounds and then treated with BLM in the absence of free acridine. The results are consistent with an increase in BLM susceptibility conferred by acridine intercalation. It is likely that the intercalating agents increase the access of BLM to the minor groove of DNA, where it abstracts a hydrogen from the 4' position of deoxyribose, creating a free radical that is processed into strand breaks.

* To whom correspondence should be addressed. Tel: +1 508 793 3416; Fax: +1 508 793 2696; Email: ghoffmann{at}holycross.edu

Received on December 31, 2008; revised on March 8, 2009; accepted on March 29, 2009.


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