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

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,N-4-(N-4-alpha-hydroxyethano)cytosine and the product of its dehydration, 3,N-4-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.