Modulation by caffeine of enhanced postreplication repair in mammalian cells treated with N-acetoxy-acetylaminofluorene.

As shown previously, newly synthesized DNA from Chinese hamster, excision proficient and excision deficient xeroderma pigmentosum (XP) cells treated with split doses of N-acetoxy-acetylaminofluorene (AAAF) or ultraviolet radiation (uv) is larger in size than DNA from cells treated with only the single dose. In this report we determined the effects of caffeine, an inhibitor of postreplication repair, upon enhancement of repair by a split dose treatment with AAAF. Caffeine was added to cells either immediately following the first or the second dose of AAAF and the size of newly synthesized DNA was determined by alkaline sucrose gradient sedimentation. Results showed that: (a) the DNA from V79 and XP cells incubated with caffeine between the first and second dose of AAAF was smaller in size than DNA from cells not incubated with caffeine; (b) caffeine exhibited a lesser effect when added after the second dose during the pulse-chase; and (c) caffeine has little effect upon daughter DNA of normal human cells treated with single or split doses of AAAF. These data indicate that caffeine interferes with the enhancement of postreplication repair in V79 and XP cells treated with AAAF.