Effect of caffeine on cell killing, mutation induction, DNA repair, and DNA synthesis after treatment with ethylnitrosourea.

The effect of caffeine on cell killing, mutation induction, DNA repair, and inhibition of DNA synthesis was investigated in a clonal derivative of M3-1 Chinese hamster cells after treatment with N-ethyl-N-nitrosourea (ENU). Caffeine enhanced cell killing but had no effect on the mutation frequency/viable cells for the two genetic markers, 6-thioguanine resistance and ouabain resistance. The removal of ethylated purine bases from DNA was as follows: most of the 3-ethyladenine was lost in 20 h (greater than 85%) and approximately 45% of the 7-ethylguanine was lost in 45 h, whereas 75--93% of the O6-ethylguanine was still present at this time. Caffeine did not seem to influence these rates significantly. The ENU-induced inhibition of DNA synthesis was reversed by caffeine. It is concluded that the potentiation of ENU-induced cell killing by caffeine is caused by the increased frequency of DNA replication past damaged sites in parental DNA.