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.