Spontaneous and induced sister chromatid exchanges in the blood lymphocytes of healthy persons and of xeroderma pigmentosum patients exposed to the inhibitors of DNA repair and replication caffeine, 3-methoxybenzamide and novobiocin

The frequency of sister chromatid exchanges (SCEs), both spontaneous and induced by UV-light, X-rays, mitomycin C and ethylmetansulphonate (EMS), has been investigated in cultured human peripheral blood lymphocytes. Besides, frequency of spontaneous and induced SCEs was studied under the action of the inhibitors of topoisomerase II, polymerase poly(ADP-ribose), and DNA repair, i. e. novobiocin, 3-metoxybenzamide, and caffeine, respectively. It is shown that the base-line SCEs in lymphocytes of the patient with xeroderma pigmentosum II (XP2LE) is dramatically higher compared to that in normal and pigmented xerodermoid cells (XP3LE). The above inhibitors of DNA synthesis and repair enhance the rate of spontaneous SCEs in normal, XP2LE and XP3LE cells. UV-, X-ray and chemical mutagens induced an increased frequency of SCEs in these cells. Simultaneous treatment with mutagenes and inhibitors of DNA synthesis and DNA repair enhanced the rate of SCEs in lymphocytes of healthy donors and in the XP3LE patient. The frequency of the XP2LE cells. Novobiocin, 3-MBA and caffeine significantly decreased the frequency of SCEs in mitomycin C- and EMS-treated XP2LE lymphocyte, which nevertheless was much higher than that in normal cells treated with the same agents.