Damage and repair of mouse lung DNA induced by 1-nitropyrene

The induction of DNA single-strand breaks (SSB), the repair of SSB, and the role of cell turnover in the removal of SSB were determined in mouse lung following intratracheal instillation of 1-nitropyrene (1-NP). Cellular DNA was prelabeled with [3H]thymidine in neonate and adult mice. 1-NP was administered to labeled neonate mice after they became adults and to the adult mice that were labeled when adults. 1-NP induced a dose-related increase in SSB (10-22 times control rate) as early as 2 h after 1-NP administration. The mice labeled as neonates were more sensitive to SSB induction by 1-NP and had a faster repair rate than mice labeled when adults. By one week after 1-NP administration, the levels of SSB in both groups of mice were similar to controls. The half-lives for DNA turnover in mice prelabeled as neonates and in mice prelabeled when adults were approximately 22 and approximately 9 days, respectively, at the time of 1-NP treatments. These data indicate that both highly proliferative cell populations and populations with lower rates of proliferation are amenable to 1-NP-induced DNA lesions. The rate of cell DNA turnover suggests that active DNA repair processes are involved in the removal of DNA lesions. The slower rate of DNA repair coupled with a relatively high rate of cell division in the rapid proliferative cells suggest that these cells may be involved in the induction of cancer in animals after 1-NP administration.