Comparison of Anti-genotoxic Activities of Dibenzoylmethane, 1,3-Indandione and 2-(Methylmercapto)benzimidazole in Bacteria and Human Cells.

Abstract

The nucleophilic compounds, diacylmethanes and thioethers, are potential scavengers of reactive electrophilic carcinogens. We have previously reported that some diacylmethanes inhibit the mutagenicities in Salmonella, and the in vitro nucleic acid-binding of some carcinogens. The present study extended the investigation to a mammalian system using unscheduled DNA synthesis (UDS) as an end-point. The amount of dibenzoylmethane (DBM), 1,3-indandione (IDD) and 2-(methylmercapto)benzimidazole (TE) were 0.1, 0.5 and 1 μmol/plate in the Ames’ test and were 0.1 and 1 mM in the UDS test. In the Ames’ test, DBM inhibited the mutagenicity of 2-nitrofluorene (2-NF) and 4-nitroquinoline-N-oxide (4-NQO), and IDD inhibited only that of 2-NF. TE did not inhibit the mutagenicity of either 2-NF or 4-NQO. The induction of UDS in a human urothelial cell line, HCV-29, with 4-NQO or N-hydroxy-2-acetylaminofluorene (N-OH-AAF) was inhibited by IDD and TE. DBM slightly inhibited the UDS-induction with N-OH-AAF, but not with 4-NQO.The inhibition in the Ames’ test and UDS system was dose-related with respect to the inhibitory agents. These results suggest that, in addition to scavenging of reactive carcinogens, other mechanisms, such as metabolism, may also be involved in the inhibition of genotoxicity. This may account for the differences in the inhibitory activities in bacteria and mammalian cells.