DNA excision in repair proficient and deficient human cells treated with a combination of ultraviolet radiation and acridine mustard (ICR-170) or 4-nitroquinoline 1-oxide.
Excision repair was measured in normal human and xeroderma pigmentosum group C fibroblasts treated with ultraviolet radiation and the carcinogens acridine mustard (ICR-170) or 4-nitroquinoline 1-oxide (4NQO) by the techniques of unscheduled synthesis, photolysis of bromodeoxyuridine incorporated into parental DNA during repair, and assays of sites sensitive to ultraviolet (UV)-endonuclease. Doses of ICR-170 and 4NQO, low enough not to inhibit unscheduled DNA synthesis (UDS), caused damage to DNA that was repaired by a long patch type mechanism and the rates of UDS decreased rapidly in the first 12 h after treatment. Repair after a combined action of UV plus ICR-170 or UV plus 4NQO was additive in normal cells and no inhibition of loss of endonuclease sensitive sites was detected. In xeroderma pigmentosum (XP) C cells there was less repair after UV plus ICR-170 than after each treatment separately; whereas there was an additive effect after UV plus 4NQO and no inhibition of loss of endonuclease sensitive sites. The results indicate that in normal human fibroblasts there are different rate limiting steps for removal of chemical and physical damages from DNA and that XP cells have a different repair system for ICR-170, not just a lower level, than normal cells. Possibly the same long patch repair system works on 4NQO damage in both normal and XP cells.
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004260:DNA Repair / Q000187:drug effects* / Q000528:radiation effects; D004720:Endonucleases / Q000494:pharmacology; D005347:Fibroblasts; D006801:Humans; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology*; D009600:Nitroquinolines / Q000494:pharmacology*; D010782:Photolysis; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000378:metabolism*
D009588:Nitrogen Mustard Compounds; D009600:Nitroquinolines; D015112:4-Nitroquinoline-1-oxide; D004247:DNA; D004720:Endonucleases; D001973:Bromodeoxyuridine