Distribution of DNA-bound carcinogen 4-nitroquinoline 1-oxide and of repair-synthesized DNA in chromatin of WI-38 cells.

Distribution of DNA-bound 4-nitroquinoline 1-oxide (4NQO) and repair-synthesized DNA after treatment with 4NQO in chromatin was investigated with human diploid fibroblast WI-38. Cells were incubated with [3H] 4NQO, and sites of binding on chromatin DNA were analyzed either by sensitivity to micrococcal nuclease or DNase I, or by fractionation of chromatin on sucrose gradient centrifugation. The results showed that 4NQO preferentially binds to DNA of linker region of chromatin, but the binding was random with respect to transcriptional activity of chromatin. The distribution of repair-synthesized DNA in chromatin damaged by 4NQO was also studied by similar experiments. [3H] Thymidine incorporated into repaired DNA was more sensitive to nucleases, but distributed almost equally among DNAs of chromatin subfractions with different transcriptional activity.