Mutagenesis and repair of DNA damage caused by nitrogen mustard, N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU), streptozotocin, and mitomycin C in E. coli.
Cytotoxicity and mutagenesis by streptozotocin, BCNU, nitrogen mustard, and mitomycin C were evaluated in E. coli mutants deficient in SOS repair, SOS-mediated mutagenesis, the adaptive response, and mutants that engage in aberrant mismatch repair. The results demonstrate that premutagenic lesions are caused by nitrogen mustard, BCNU and streptozotocin that are not repaired by ada or recognized by umuDC. Further, recA mutants were hypomutable after exposure to nitrogen mustard, BCNU, and streptozotocin compared to wild type. With the exception of the monofunctional nitrosourea, streptozotocin, both recA and uvrA gene products contribute to the repair of DNA damage caused by the alkylating agents tested. In the case of streptozotocin, although recA mutants were more sensitive than wild type, uvrA mutants were not. Moreover, while ada and alkA E. coli mutants showed increased sensitivity to streptozotocin, they were not more sensitive to the other alkylating agents evaluated.
D002330:Carmustine / Q000494:pharmacology*; D004249:DNA Damage; D045647:DNA Glycosylases; D004260:DNA Repair / Q000187:drug effects*; D004269:DNA, Bacterial / Q000187:drug effects* / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D005798:Genes, Bacterial; D008466:Mechlorethamine / Q000494:pharmacology*; D008780:Methyltransferases / Q000502:physiology; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology*; D009699:N-Glycosyl Hydrolases / Q000502:physiology; D011938:Rec A Recombinases / Q000502:physiology; D013014:SOS Response, Genetics / Q000187:drug effects*; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific); D013311:Streptozocin / Q000494:pharmacology*
D004269:DNA, Bacterial; D008937:Mitomycins; D008466:Mechlorethamine; D016685:Mitomycin; D013311:Streptozocin; D008780:Methyltransferases; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific); D011938:Rec A Recombinases; C021565:3-methyladenine-DNA glycosylase; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D002330:Carmustine