Reduced DNA repair capacity and increased cytotoxicity following split doses of the mutagen 4-nitroquinoline-1-oxide in cultured human cells.
Cultured human fibroblasts were exposed to single doses of 4-nitroquinoline-1-oxide(4NQO) and to two equimolar doses of 4NQO at intervals varying from 0.5 to 12 h. DNA repair synthesis as measured by an unscheduled uptake of tritium-labelled thymidine ([3-H]TdR), cell survival as estimated by the clone-forming capacity, and frequency of chromosome aberrations were used as endpoints. Cells respond with a reduced level of DNA repair synthesis when the second 4NQO dose (5 X 10 minus 7 or 1 X10-minus 7 M) is given within 3 h of the first 4NQO dose. If the interval between the two doses is 5 h or more, the level of DNA repair synthesis which is induced by the second 4NQO dose is comparable to that following a single 60-min 4NQO application. In this 3-h period the cultured cells show an increased sensitivity to the lethal effect and chromosome-damaging action of the second 4NQO dose. The reduced period of DNA repair capacity seems to increase the mutagenic effect of the chemical carcinogen.
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology*; D002470:Cell Survival; D002478:Cells, Cultured / Q000187:drug effects*; D002869:Chromosome Aberrations; D002999:Clone Cells / Q000187:drug effects; D004260:DNA Repair; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009153:Mutagens / Q000494:pharmacology*; D009600:Nitroquinolines / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014316:Tritium
D009153:Mutagens; D009600:Nitroquinolines; D014316:Tritium; D015112:4-Nitroquinoline-1-oxide; D013936:Thymidine