Defective repair of a class of 4NQO-induced alkali-labile DNA lesions in xeroderma pigmentosum complementation group A fibroblasts.
Normal human or xeroderma pigmentosum complementation group A (XP-A) fibroblasts were exposed to various concentrations of either 4-nitroquinoline 1-oxide (4NQO) or its 3-methyl derivative, and the rates of repair of the alkali-labile lesions induced in DNA by each agent were monitored over a period of 24 h post-treatment incubation. The data indicate that 4NQO induces at least two major classes of alkali-labile lesions into human DNA; one class disappears rapidly from the DNA of both normal and XP-A fibroblasts, while the other class undergoes repair at a relatively slow rate in normal cells, but is not removed at all in the excision-deficient cells. Methylation of 4NQO at the 3-position appears to abolish the induction of the latter class of alkali-labile lesions, whereas the rapidly removed lesions are still being induced.
D015108:4-Hydroxyaminoquinoline-1-oxide / Q000494:pharmacology; D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology* / Q000031:analogs & derivatives; D004260:DNA Repair / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009600:Nitroquinolines / Q000494:pharmacology*; D014983:Xeroderma Pigmentosum / Q000378:metabolism*
D009600:Nitroquinolines; C036910:3-methyl-4-nitroquinoline 1-oxide; D015108:4-Hydroxyaminoquinoline-1-oxide; D015112:4-Nitroquinoline-1-oxide