title: Mutagenic effects of gamma-rays and incorporated 8-3H-purines on extracellular lambda phage: influence of mutY and mutM host mutations.
abstract: The lethal and mutagenic effects on phage lambdacI857 of 60Co gamma-rays and of decay of 3H incorporated into phage DNA both as 8-3H-deoxyadenosine and 8-3H-deoxyguanosine (using 8-3H-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 mutant 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 3H decay in position 8 of purine residues 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 effect. The lethal effects of both gamma-rays and tritium decay virtually did 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 3H decay in purine residues of phage DNA. The efficiencies of mutagenic action of 3H-purines E(m) (frequencies of c-mutations per one 3H decay in phage 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 efficiencies E(m) for gamma-rays were nearly identical in the M(+)Y(+) and M(-)Y(+) hosts, 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 glycosylases are important for prevention of mutations caused not only by spontaneous oxidation of guanine residues, but also by ionizing radiation or by decay of 3H incorporated into purine bases of DNA; (2) the MutY and MutM enzymes functionally cooperate in elimination of mutagenic damages induced by these agents.
authors.affiliation: Division of Molecular and Radiation Biophysics, Petersburg Nuclear Physics Institute, Russian Academy of Sciences, 188350, Gatchina, Russian Federation.
authors.forename: L V
authors.initials: LV
authors.lastname: Konevega
authors.forename: V L
authors.initials: VL
authors.lastname: Kalinin
mesh_terms: D010582:Bacteriophage lambda / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D045647:DNA Glycosylases; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects; D004279:DNA, Viral / Q000528:radiation effects; D043382:DNA-Formamidopyrimidine Glycosylase; D004307:Dose-Response Relationship, Radiation; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D029968:Escherichia coli Proteins; D005720:Gamma Rays; D005787:Gene Frequency / Q000528:radiation effects; D009154:Mutation / Q000235:genetics; D009699:N-Glycosyl Hydrolases / Q000235:genetics*; D011687:Purines / Q000378:metabolism*; D014316:Tritium; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000528:radiation effects
chemical_list: D004279:DNA, Viral; D029968:Escherichia coli Proteins; D011687:Purines; D014316:Tritium; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; C061738:mutY adenine glycosylase; D043382:DNA-Formamidopyrimidine Glycosylase; C468610:DNA-formamidopyrimidine glycosylase, E coli