Reduction of sister chromatid exchange frequency with time after mutagen exposure in Chinese hamster ovary cells in the presence of 3-aminobenzamide

Abstract

3-Aminobenzamide (3AB) is a potent inhibitor of poly (ADP-ribose) synthesis and has been reported to inhibit DNA repair. Inhibition of poly(ADP-ribose) synthesis by 3AB results in a potentiation of the cytotoxic effects of alkylating agents and synergistically increases the frequency of sister chromatid exchanges (SCEs) induced in Chinese hamster ovary cells by methyl methanesulfonate (MMS). Experiments were carried out to determine if this synergism was related to an inhibition of the repair or the removal of SCE-forming lesions by 3AB. Cells were treated with MMS or ethyl nitrosourea (ENU) and either held in a nonproliferative state or maintained in exponential growth for up to 48 hr before SCE frequencies were measured. During this time, the SCE frequency decreased greatly. 3AB did not affect this decrease in either cycling or noncycling cells. Furthermore, 3AB appears to exert its effect only in cycling cells when bromodeoxyuridine is present. Therefore, the synergism between 3AB and alkylating agents in the induction of SCEs is unrelated to effects of 3AB on the repair or removal of SCE-forming lesions.