Mutagenic effects of gamma-rays and incorporated 8-H-3-purines on extracellular lambda phage: influence of mutY and mutM host mutations

The lethal and mutagenic effects on phage lambda cI857 of Co-60 gamma-rays and of decay of H-3 incorporated into phage DNA both as 8-H-3-deoxyadenosin e and 8-H-3-deoxyguanosine (using 8-H-3-adenine as a labelled DNA precursor ) were studied on four isogenic Escherichia coli strains: AB1157 M+Y+ (wild type, mutM(+) mutY(+)), AB1157 M-Y+ (mutM::kan mutY(+) mutant deficient in the formamidopyrimidine-DNA glycosylase MutM), AB1157 M+Y- (mutM(+) mutY m utant deficient in the A:G mismatch DNA glycosylase MutY), and AB1157 M-Y- (mutM::kan mutY double mutant deficient in both DNA glycosylases). The main products of transmutation component of H-3 decay in position 8 of purine r esidues are 8-oxo-7,8-dihydroadenine (8-oxoA) and 8-oxo-7,8-dihydroguanine (8-oxoG), the latter being responsible for the most part of the mutagenic e ffect. The lethal effects of both gamma-rays and tritium decay virtually di d not depend on the repair phenotypes of the host strains used. Therefore, the MutM and MutY glycosylases are not involved in the repair of lethal DNA damages induced by ionizing radiation or by the transmutation component of H-3 decay in purine residues of phage DNA. The efficiencies of mutagenic a ction of H-3-purines E-m (frequencies of c-mutations per one H-3 decay in p hage genome) were 2.4-, 3.8- and 55-fold higher in the M-Y+, M+Y- and M-Y- mutants, respectively, in comparison to the wild-type host. The mutagenic e fficiencies E-m for gamma-rays were nearly identical in the M+Y+ and M-Y+ h osts, but were increased 1.8- and 8.3-fold, respectively, in the M+Y- and M -Y- mutants. These data suggest that: (1) the MutY and MutM DNA glycosylase s are important for prevention of mutations caused not only by spontaneous oxidation of guanine residues, but also by ionizing radiation or by decay o f H-3 incorporated into purine bases of DNA; (2) the MutY and MutM enzymes functionally cooperate in elimination of mutagenic damages induced by these agents. (C) 2000 Published by Elsevier Science B.V. All rights reserved.