Poly (ADP-ribose) polymerase-1 deficiency does not affect ethylnitrosourea mutagenicity in liver and testis of lacZ transgenic mice.

摘要: Poly (ADP-ribose) polymerase-1 (Parp1) has been implicated in DNA base excision repair, single- and double-strand break repair pathways, as well cell death by apoptosis or necrosis. We used Parp1(-/-) lacZ plasmid-based transgenic mice to investigate whether Parp1 deficiency influences the vivo mutagenic clastogenic response alkylating agent N-ethyl-N-Nitrosourea (ENU) somatic germ-cell tissues. The comparison of mutant frequencies (MFs) between Parp1(+/+) showed that ablation does not affect spontaneous ENU-induced MFs liver testis. In addition, spectrum mutations was dependent on status, given similar spectra, consisting mostly point a small fraction deletions/insertions, wereobserved organs both mice. Sequencing revealed consistent significant increase A:T --> T:A substitutions, typically induced ENU. Overall, we observed neither frequency nor demonstrated specificity could be attributed impairment organs. analysis micronucleus peripheral blood reticulocytes ENU had strong cytotoxic effect only. present data suggest that, at whole-organism level, Parp1-independent mechanisms may operative removal lesions highly damaged cells preferentially committed when is inactivated.