Heterogeneous repair of methylnitrosourea-induced alkali-labile sites in different DNA sequences

The repair of DNA damage induced by methylnitrosourea (MNU) in restriction fragments containing the dihydrofolate reductase (DHFR) gene in Chinese hamster ovary cells was compared to that in equal size restriction fragments containing a nontranscribed flanking sequence 3' to the DHFR gene or the c-fos gene. Following exposure to 10(-3) M MNU, restriction fragments containing either the DHFR gene or the 3' flanking sequence had similar amounts of alkali labile sites, approximately 2 sites/restriction fragment. Fragments encompassing the c-fos gene had less than 2 breaks/fragment. Twenty-four h after exposure to MNU a consistent, but slight and not statistically significant, difference was seen with more adducts removed from the DHFR gene than the 3' flanking sequence. No repair was detected in the c-fos containing fragments. In addition, the repair of N7-methylguanine in the overall genome was assessed by use of a 32P end-labeling technique. Seventy % of this major alkylation product was repaired after 24 h. These findings establish that repair heterogeneity occurs in Chinese hamster ovary cells after exposure to MNU.