Evidence for a fast repair of apurinic sites induced by N-nitroso-dimethylamine in rat liver DNA.

Sprague Dawley male rats were treated with N-nitroso-dimethylamine and the damage induced in liver DNA was investigated using the in vivo DNA alkaline elution assay. Determination of the number of single stranded breaks after different incubation periods in alkali showed that most of them (approximately equal to 95%) were alkali-labile sites, with a half-life of about 33 min, as expected for apurinic sites. The extent of DNA methylation was calculated, by assuming depurination of N-7-methylguanine to be the rate-limiting step for breakdown of DNA. The amount of DNA fragmentation observed accounted for only one fifth of N-7-methylguanine. The calculation could be made to correspond to the extent of methylation determined experimentally, by assuming the occurrence of a fast repair in vivo of apurinic sites (t1/2 approximately equal to 18 min). Our hypothesis of a fast repair of apurinic sites is in agreement with the analysis of data of Peterson et al. (1974). Moreover, the rate of repair required by the level of spontaneous depurination of normal guanine at neutral pH and 37 degree C, agrees satisfactorily with our estimations.