The effect of methylated oxypurines on the size of newly-synthesized DNA and on the production of chromosome aberrations after UV irradiation in Chinese hamster cells

Abstract

A comparison has been made, in Chinese hamster cells, of the ability of various methylated oxypurines to inhibit post-replication repair of DNA after UV irradiation and to potentiate UV-induced chromosome aberrations. DNA synthesized in UV-irradiated cells contains gaps, which are subsequently sealed by a process termed post-replication repair. In rodent cells this process is inhibited by caffeine and its analogues. This has been quantitated by measuring the molecular weight of the DNA synthesized in UV-irradiated cells during a 4-h pulse-labelling period in the presence or absence of inhibitors--the lower molecular weight the greater the inhibition. Eight methylated oxypurines were tested; caffeine and chlorocaffeine were always the most potent inhibitors, tetramethyluric acid was inactive, and the other five derivatives (methoxycaffeine, ethoxycaffeine, paraxanthine, theobromine and theophylline) had intermediate effects. Measurements of the potentiation of UV-induced chromosome aberrations showed that treatments with caffeine or chlorocaffeine again had the greatest effects, tetramethyluric acid and also theophylline had no potentiating activity, and methoxycaffeine was intermediate. This correlation between effects at the molecular and cytological levels is consistent with the hypothesis that the inhibition of post-replication repair by methylated oxypurines gives rise to the increased production of chromosome aberrations.