COMUTAGENIC EFFECTS OF 3-AMINOBENZAMIDE IN CHINESE-HAMSTER OVARY CELLS

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (4) , 1556-1559
Abstract
Inhibition of poly (ADP-ribose) synthesis by agents such as 3-aminobenzamide (3-AB) potentiates the cytotoxic, carcinogenic and clastogenic effects of certain DNA-damaging agents. Experiments were carried out in Chinese hamster ovary cells to compare chromosome aberration production and cytotoxicity with the induction of somatic mutations at the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and Na-K ATPase loci after treatment with 3-AB in combination with certain monofunctional alkylating agents. On its own, 1-10 mM concentrations of 3-AB were not mutagenic, reduced plating efficiencies 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 N-methyl-N''-nitro-N-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 mutations). All the effects were dose-dependent. Larger absolute increases were found with 10 mM 3-AB as compared to 1 mM 3-AB and 2 mM EMS as compared to 1 mM EMS. The 3-AB-mediated increases in 6-thioguanine-resistant cells, which are often deletion mutations, and the lack any increase in the frequency of ouabain-resistant cells, which can only arise through point mutation induction, along with the increases in chromosome aberration freqeuncy suggests that 3-AB increases the frequency of deletion mutation by increasingly the frequency and duration of DNA strand breaks.

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