Metabolism of 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) by Human CYP1B1 Genetic Variants

Abstract

ABSTRACT:Human cytochrome P450 1B1 (CYP1B1) plays a critical role in the metabolic activation of a variety of procarcinogens, including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). The existence of human CYP1B1 missense genetic variants has been demonstrated, but their activities in metabolizing PhIP are unknown. In this study, we expressed 15 naturally occurring CYP1B1 variants (with either single or multiple amino acid substitutions) and determined their activity changes in metabolizing PhIP to its two major metabolites, 2-hydroxyamino-PhIP and 4-hydroxy-PhIP.

Protective Effects of Chrysin Against Drugs and Toxic Agents

“…45 2-Amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine. Numerous studies have been shown that 2-amino-1-methyl-6phenylimidazo [4, 5-b] pyridine (PhIP), the most abundant heterocyclic amines, 46 is a potent mutagen and tumourigenic in animal models. Chrysin supplementation protected the liver against PhIP-induced mutagenic effects by inducing UDPglucuronosyltransferase and/or inhibiting sulfotransferase in HepG2 cells.…”

Xenobiotic Metabolizing Genes, Meat-Related Exposures, and Risk of Advanced Colorectal Adenoma

“…Functionality of these variants in relation to PhIP is not well-characterized and, thus far, has been studied only in combination with other SNPs for this gene [47]. Another possible reason for an interaction between PhIP and the CYP1B1 rs10012 variant is the relatively high correlation between PhIP and B[a]P (0.58) in our population.…”

The Effect of Flavonoids in Soybean Products in Lymphocytes from IBD and Colon Cancer Patients After Treatment with Food Mutagens and Hydrogen Peroxide

“…After in vitro treatment with IQ and PhIP an increase in DNA damage in lymphocytes was observed in our study but confounding factors such as diet, smoking and drinking habits did not seem to influence this response, even though numerous environmental and lifestyle compounds can have an impact on the exposure, metabolism and cell proliferation response of HCA (Felton et al, 2004). Nevertheless, in most of the cases the damage was similarly distributed and the general response to treatment may still be dependent on possible dietary interactions after exposure to food mutagens and individual factors like individual susceptibility, cellular antioxidant / micronutrient levels or disease states (Airoldi et al, 2004;El-Zein et al, 2006;Ferguson and Philpott, 2008;Han et al, 2008;Pool-Zobel et al, 2004). It has been estimated that up to 90% of the cases of colorectal cancer could be prevented with life style modifications such as balanced diet, avoidance of smoking and alcohol and physical activity (Boursi and Arber, 2007).…”