Lethal effect of mitomycin C on Haemophilus influenzae.
The sensitivity of ultraviolet-sensitive strains to inactivation by mitomycin C (MC) is at the most only a factor of two greater than that of the wild type. The presence of inducible prophage has very little effect on the sensitivity. Genes which control excision of ultraviolet-induced pyrimidine dimers also control repair of MC-induced cross-links, as measured by resistance of denatured deoxyribonucleic acid (DNA) from treated cells to S1 nuclease digestion. However, endonucleolytic breaks in MC-damaged DNA, as judged by decreased single-strand molecular weight upon incubation of treated cells, are independent of these genes and probably are caused by monoadducts. After long periods of incubation there is a return to the molecular weight of untreated DNA. DNA degradation after MC treatment of various strains is not correlated with sensitivity to inactivation. Stationary-phase cells of all strains are more than twice as sensitive to MC as exponentially growing cells, and the sensitivity difference agrees with the measured difference in the number of cross-links after MC treatment of cells in the two growth stages. Evidence has been obtained that these phenomena result from differences in uptake of MC, which can be influenced by cyclic adenosine monophosphate. Small deviations in MC sensitivity from that of the wild type observed in mutants lacking the adenosine 5'-triphosphate-dependent nuclease are postulated to result from differences in MC uptake. These mutants, although no more ultraviolet sensitive than the wild type, are more sensitive to streptomycin, which also must be taken up by the cell to be effective.
D000242:Cyclic AMP / Q000378:metabolism; D004260:DNA Repair; D004269:DNA, Bacterial / Q000096:biosynthesis / Q000378:metabolism; D003851:Deoxyribonucleases / Q000096:biosynthesis; D004352:Drug Resistance, Microbial; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D008242:Lysogeny; D008937:Mitomycins / Q000378:metabolism / Q000494:pharmacology*; D009154:Mutation; D009691:Nucleic Acid Denaturation; D011830:Radiation Effects; D011995:Recombination, Genetic; D014466:Ultraviolet Rays
D004269:DNA, Bacterial; D008937:Mitomycins; D000242:Cyclic AMP; D003851:Deoxyribonucleases