Excision-repair of 4-nitroquinolin-1-oxide damage responsible for killing, mutation, and cancer.
Excision-repair of DNA base damage produced by 4-nitroquinoline-1-oxide (4NQO) was compared in Escherichia coli, human cells, and mouse cells. Paper chromotography of acid hydrolysates of DNA extracted from cells treated with 3H-labeled 4NQO revealed four peaks; two kinds of 4NQO-guanine adduct, one kind of 4NQO-adenine adduct, and free 4-aminoquinoline-1-oxide (4AQO). About 80% of the initially formed 4NQO-purine adducts were excised from DNA in E. coli uvrA+ cells during 60 min postincubation, but not at all in uvrA- (excisionless for uv damage) cells. Normal human cells excised about 60% of 4NQO-purine adducts during 24 hr postincubation, but xeroderma pigmentosum (excisionless) cells did not. A mouse cell line susceptible to repair of 4NQO-induced pretransformational damage also showed excision-repair ability for the 4NQO adducts. From these and other results, we conclude that the 4NQO-purine adducts and unstable 4NQO-guanine products (which release 4AQO) are, like pyrimidine dimers, repairable by excision-repair universal among E. coli, mouse, and human being, and that unexcised ones are probably the major cause of killing, mutation, and cancer.
D015112:4-Nitroquinoline-1-oxide / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects*; D004269:DNA, Bacterial / Q000096:biosynthesis; D004926:Escherichia coli / Q000378:metabolism / Q000528:radiation effects; D007700:Kinetics; D008970:Molecular Weight; D009154:Mutation / Q000187:drug effects*; D009369:Neoplasms / Q000139:chemically induced*; D009600:Nitroquinolines / Q000494:pharmacology*; D011830:Radiation Effects; D014466:Ultraviolet Rays
D004269:DNA, Bacterial; D009600:Nitroquinolines; D015112:4-Nitroquinoline-1-oxide