Induction of single-strand breaks plus alkali-labile bonds by N-nitrosoureas in rat tissues in vivo: ethylnitrosourea versus benzylnitrosourea.

Alkaline sucrose sedimentation procedures were used to quantitate the amount of single-strand breaks plus alkali-labile bonds (SSB + ALB) induced and repaired following a single intraperitoneal injection of the neurocarcinogen N-ethyl-N-nitrosourea (ENU) and its non-neurocarcinogenic analog N-benzyl-N-nitrosourea (BNU) in the brain, liver and kidney of female Sprague-Dawley rats. SSB + ALB were measured and used as an indicator of apurinic/apyrimidinic sites, phosphotriesters and in situ breaks. ENU induced a dose-dependent increase in the number of SSB + ALB at the doses studied (0, 0.39, 0.77, 1.54 mmoles/kg) in all 3 tissues. At 1 h postinjection with 0.77 mmoles/kg of these compounds there were 50-70% fewer breaks induced by BNU than ENU. The SSB + ALB induced by ENU persisted over a 7-day period, while those induced by BNU did not. Thus, these studies showed that 2 homologues of nitrosoureas, ENU and BNU, exhibited different potentials to induce and to persist SSB + ALB in vivo.