Comutagenic Effects of 3-Ammobenzamide in Chinese Hamster Ovary Cells1

Inhibition of poly (ADP-ribose) synthesis by agents such as 3aminobenzamide (3-AB) potentiates the cytotoxic, carcinogenic, and clastogenic effects of certain DNA-damaging agents. Exper iments were carried out in Chinese hamster ovary cells to com pare chromosome aberration production and cytotoxicity with the induction of somatic mutations at the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and sodium-potassium ATPase loci after treatment with 3-AB in combination with certain monofunctional alkylating agents. On its own, 1 to 10 mw con centrations of 3-AB were not mutagenic, reduced plating effi ciencies only slightly, and produced a small elevation in the frequency of chromatid aberrations. In combination with ethyl methanesulfonate (EMS), 3-AB increased cytotoxicity and the frequency of alkylation-induced chromatid aberrations. 3-AB also increased the frequency of EMS and W-methyl-A/'-nitro-W-nitrosoguanidine-induced 6-thioguanine-resistant cells (a marker for the HGPRT" phenotype). It had no effect on the frequency of EMS-induced ouabain-resistant cells (a marker for ATPase mu tations). All the effects were dose dependent. Larger absolute increases were found with 10 mw 3-AB as compared with 1 mw 3-AB and with 2 mw EMS as compared to 1 mw EMS. The 3AB-mediated increases in 6-thioguanine-resistant cells, which are often deletion mutations, and the lack of any increase in the frequency of ouabain-resistant cells, which can only arise through point mutation induction, along with the increases in chromo some aberration frequency, suggests that 3-AB increases the frequency of deletion mutations by increasing the frequency and duration of DMA strand breaks.