Trans-dominant inhibition of poly(ADP-ribosyl)ation potentiates alkylation-induced shuttle-vector mutagenesis in Chinese hamster cells

摘要: In most eukaryotic cells, the catalytic activation of poly(ADP-ribose) polymerase (PARP) represents one earliest cellular responses to infliction DNA damage. To study biological function(s) poly(ADP-ribosyl)ation, we have established stable transfectants (COM3 cells) SV40-transformed Chinese hamster cell line C060 which conditionally overexpress PARP DNA-binding domain upon addition dexamethasone. We could demonstrate that overexpression, leads trans-dominant inhibition potentiates cytotoxicity alkylation treatment and γ-radiation [21]. Likewise, carcinogen-induced gene amplification, viewed as a manifestation genomic instability, was potentiated by overexpression [22]. Recently, studied effect on mutagenesis employing shuttle-vector assay in mutagen-exposed plasmid pYZ289 is electroporated into COM3 cells. show dexamethasone-induced cells mutagenicity alkylating agent N-methyl-N-nitrosourea, while no dexamethasone mutation frequency recorded control lacking transgene. Taken together, our results further substantiate role poly(ADP-ribosyl)ation maintenance integrity stability under conditions genotoxic stress.