Induction of the Escherichia coli UVM response by oxidative stress.

UVM (ultraviolet modulation of mutagenesis) is a recently described recA-independent, inducible mutagenic phenomenon in which prior UV irradiation of Escherichia coli cells strongly enhances mutation fixation at a site-specific 3-N4-ethenocytosine (epsilon C) lesion borne on a transfected single-stranded M13 DNA vector. Subsequent studies demonstrated that UVM is also induced by alkylating agents, and is distinct from both the SOS response and the adaptive response to alkylation damage. Because of the increasing significance being attributed to oxidative DNA damage, it is interesting to ask whether this class of DNA damage can also induce UVM. By transfecting M13 vector DNA bearing a site-specific epsilon C lesion into cells pretreated with inducing agents, we show here that the oxidative agent H2O2 is a potent inducer of UVM, and that the induction of UVM by H2O2 does not require oxyR-regulated gene expression. UVM induction by H2O2 appears to be mediated by DNA damage, as indicated by the observation of a concomitant reduction in cellular toxicity and UVM response in OxyRc cells. Available evidence suggests that UVM represents a generalized cellular response to a broad range of chemical and physical genotoxicants, and that DNA damage constitutes the most likely signal for its induction.