3 Aminobenzamide, an inhibitor of poly ADP-ribose polymerase, decreases the frequency of alkaline labile lesions and increases growth in human fibroblasts exposed to 3-methyl 4-nitroquinoline 1-oxide

Abstract

Normal human fibroblasts [HSBP or 1BR cells] exposed to the mutagen 3-methyl 4-nitroquinoline 1-oxide (3me4NQO) were additionally incubated with or without the inhibitor of poly ADP-ribose polymerase, 3 aminobenzamide (3AB) either during or after mutagen treatment. The number of single strand DNA breaks detectable by alkaline sucrose sedimentation at any given time after exposure to this mutagen was reduced by the prior addition of 3AB, regardless of whether this drug was present during or after mutagen exposure. This effect is reversible upon 3AB removal. Cell survival, as analysed by cell growth, was increased if cells were treated for 1 h with 3AB directly following a 30 min exposure to 3-me4NQO. The data presented suggest an additional role for poly ADP ribose polymerase in DNA repair other than that of inhibiting the increase in ligase II, which occurs after exposure to monofunctional alkylating agents.