Inhibitory effect of theophylline on repair of potentially lethal MMS-induced damages to DNA in V79 cells.

In a study of Chinese hamster V79 cells growing in the presence of sublethal concentrations of theophylline, we followed both the nature of DNA replication and the cells' response to toxic and DNA-damaging effects of methyl methanesulfonate (MMS). We found that cells cultured at low concentrations of theophylline (less than or equal to 0.3 mg/ml medium) showed deviations in the rate of DNA replication which, however, did not depress either the growth activity of the cells or their colony-forming ability. Considerable differences as against the controls appear in theophylline-cultured cells after treatment with MMS. Not only are they more sensitive to the toxic effects of this alkylating agent, but also their DNA synthesis is strikingly inhibited. More unrepaired lesions remain in parental DNA, and short fragments of daughter DNA, synthesized following cell treatment with MMS, are not elongated during a 2-h post-MMS treatment. Theophylline obviously belongs among agents inhibiting repair of potentially lethal MMS-induced DNA damages in Chinese hamster V79 cells.