Warren P M, Stich H F
Mutat Res. 1975 May;28(2):285-93. doi: 10.1016/0027-5107(75)90106-2.
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.
将培养的人成纤维细胞暴露于单剂量的4-硝基喹啉-1-氧化物（4NQO）以及间隔时间从0.5小时至12小时不等的两等摩尔剂量的4NQO。通过氚标记胸腺嘧啶核苷（[3-H]TdR）的非预定摄取来测量DNA修复合成，通过克隆形成能力估计细胞存活，并将染色体畸变频率用作终点指标。当在第一次给予4NQO剂量后的3小时内给予第二次4NQO剂量（5×10^-7或1×10^-7 M）时，细胞的DNA修复合成水平降低。如果两次剂量之间的间隔为5小时或更长时间，第二次4NQO剂量诱导的DNA修复合成水平与单次60分钟应用4NQO后的水平相当。在这3小时期间，培养的细胞对第二次4NQO剂量的致死效应和染色体损伤作用表现出更高的敏感性。DNA修复能力降低的时期似乎增加了化学致癌物的诱变作用。
