Modulation of the mutagenicity of food carcinogens by oligomeric and polymeric procyanidins isolated from grape seeds: synergistic genotoxicity withN-nitrosopyrrolidine

Oligomeric and polymeric procyanidins were isolated from grape seeds, and their antimutagenic potential against food carcinogens was evaluated in the Ames test. Both procyanidins suppressed the mutagenicity of IQ and benzo[a]pyrene but did not modulate the mutagenic activity of MNNG. At the concentrations where antimutagenic activity was expressed, the oligomeric and polymeric procyanidins inhibited the hepatic O-dealkylation of methoxy- and ethoxyresorufin. It is concluded that the antimutagenic activity exhibited by oligomeric and polymeric procyanidins is the consequence of inhibition of CYP1A-mediated bioactivation. In contrast with these findings, oligomeric and polymeric procyanidins potentiated the mutagenicity of N-nitrosopyrrolidine; the monomeric tea flavanols (+)-catechin and (−)-epicatechin also elicited the same effect. Both the flavanols and procyanidins, at the concentrations studied, failed to elicit a mutagenic response in the Ames test, either in the presence or absence of an activation system. Incorporation of catalase and superoxide dismutase to the activation system failed to prevent the synergistic effect between (+)-catechin and the nitrosamine. The mutagenic activity of N-nitrosopyrrolidine was much higher when the bacteria were grown in nutrient broth supplemented with (+)-catechin compared with bacteria grown in nutrient broth alone. It may be cautiously inferred that the synergistic genotoxicity between polyphenolics and N-nitrosopyrrolidine involves interaction of (+)-catechin with bacterial DNA, facilitating the covalent binding of the ultimate carcinogens of the nitrosamine to the DNA.