Antimutagenicity of ethanol extracts of bee glue against environmental mutagens

The antimutagenicity of ethanol extracts of bee glue (propolis) (EEBG) was evaluated, using Salmonella typhimurium strain TA98 as a test model, against two direct mutagens, 4-nitro-O-phenylenediamine (4-NO) and 1-nitropyrene (1-NP), and two indirect mutagens, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and benzo[a]pyrene (B[a]P) with S9 mix. EEBG was shown to suppress the mutagenicity of these compounds in a dose-dependent fashion. To delineate the mechanism of action of the antimutagenic effects of EEBG on the two indirect mutagens IQ and B[a]P, two possible points of blocking were considered: (1) cytochrome P-450 activity (route 1) and (2) interaction with microsome-generated proximate mutagens to generate an inactive complex (route 2). Our results clearly demonstrated, at a very low dose, remarkable suppression of the mutagenicity of both compounds by inhibiting either route 1 or route 2 pathway. Further studies indicated that EEBG was capable of inhibiting both the activities of hepatic cytochrome P-450 IA1-linked 7-ethoxyresorufin-O-deethylase (EROD) and IA 2-linked 7-ethoxycoumarin-O-deethylase (ECD) in a similar dose-dependent manner. Taken together, we demonstrated that EEBG was a good inhibitor for mutagenicity of direct mutagens, 1-NP and 4-NO, as well as for the indirect mutagens IQ and B[a]P in the presence of S9 mix via inactivation of microsomal enzyme activities (e.g. EROD and ECD) or antagonizing metabolic generation of the proximate mutagens of IQ and B[a]P.