Differential modulation of the genotoxicity of food carcinogens by naturally occurring monomeric and dimeric polyphenolics

Naturally occurring dimeric polyphenolics and their gallate esters were iso lated from grope seeds, almond fruits, and apple skin, and their ability to modulate the mutagenicity of food carcinogens was studied in the Ames test , and compared to that of the monomeric green tea flavonols, (+)-catechin a nd (-)-epicatechin. Neither the monomeric nor the dimeric polyphenols and t heir galloylated derivatives influenced the mutagenic activity elicited by the indirectly acting food carcinogens benzo[a] pyrene and 2-amino-3-methyl imidazo-[4,5f]quinoline (IQ), in the presence of a hepatic activation syste m derived from Aroclor 1254-treated rats; the only exception was the B7 dim er, which, at concentrations above 1 mu M, suppressed the mutagenicity of I Q. None of the polyphenolics modulated the mutagenic activity elicited by t he directly acting carcinogen N'-methyl-N'-nitro-nitrosoguanidine (MNNG). I n contrast, all the dimeric polyphenols and the galloylated metabolites, at concentrations over 1 mu M, potentiated the mutagenic activity induced by the indirectly acting carcinogen N-nitrosopyrrolidine, in the presence of o n activation system derived from isoniazid-treated rots. In conclusion, dim eric polyphenols and golloylated derivatives of plant origin ore unlikely t o influence the initiation stage of the carcinogenicity of chemicals throug h mechanisms that involve inhibition of their cytochrome P450-mediated bioa ctivation or scavenging of the reactive, genotoxic intermediates. (C) 2000 Wiley-Liss, Inc.