Excision-repair of 4-nitroquinolin-1-oxide damage responsible for killing, mutation, and cancer

Basic Life Sci. 1975:5B:763-71. doi: 10.1007/978-1-4684-2898-8_54.

Abstract

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.

MeSH terms

  • 4-Nitroquinoline-1-oxide / metabolism
  • 4-Nitroquinoline-1-oxide / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • DNA Repair / drug effects*
  • DNA, Bacterial / biosynthesis
  • Escherichia coli / metabolism
  • Escherichia coli / radiation effects
  • Kinetics
  • Molecular Weight
  • Mutation / drug effects*
  • Neoplasms / chemically induced*
  • Nitroquinolines / pharmacology*
  • Radiation Effects
  • Ultraviolet Rays

Substances

  • DNA, Bacterial
  • Nitroquinolines
  • 4-Nitroquinoline-1-oxide