The induction of adaptive response to alkylating agents in Escherichia coli reduces the frequency of specific C → T mutations in chloroacetaldehyde-treated M13 glyU phage

Abstract

The mutagenicity and repair of cytosine adducts formed in reactions of chloroacetaldehyde (CAA), a metabolite of the human carcinogen vinyl chloride, have been studied. The treatment of single-stranded DNA M13 JCM15472 (glyU313) phage with CAA and subsequent transfection of Escherichia coli K-12 JC15419 (trpA461) tester strain resulted in a dose-dependent increase of phage C ↑ T transitions and a decrease of phage survival. The induction of the adaptive response to alkylating agents in bacterial cells significantly decreased the frequency of examined C ↑ T transitions and increased phage survival. The results indicate that both CAA adducts to cytosine, the initially formed 3, N⁴- (N⁴-α-hydroxy-ethano)cytosine and the product of its dehydration, 3, N⁴ -ethenocytosine, provoke C ↑ T transitions and are repaired in adapted bacteria. The role of 3-methyladenine-DNA glycosylase II, which is a part of the adaptive response system in E. coli, in excision of CAA adducts to cytosine, is discussed.