Human prostate epithelial cells metabolize chemicals of dietary origin to mutagens

Human prostate epithelial cells from a 17- and 42-year-old donor and designated as HuPrEC(17) and HuPrEC(42), were used to metabolize 2-aminodipyrido[1,2-a:3',2-d]imidazole (Glu-P-2), 2-amino-3,8-dimethylimidazo[4.5-f]quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP). The ability of the HuPrEC to metabolize these chemicals was measured as the mutagenicity of the test chemicals in V79 cells. Arylamine N-acetyltransferase (NAT1 and NAT2) genotype and activity, cytochrome P4501A2 (CYP1A2) activity and genotype, and glutathione S-transferase (GSTM1, GSTP1 and GSTT1) genotype were measured. HUPrEC(17) expressed a slow form of NAT1 (*4/*3) and an intermediate form of NAT2 (*4/*6) while HuPrEC(42) expressed the rapid form of NAT1 (*10/*10) and an intermediate form of NAT2 (*4/*5). Both had comparable NAT1 activity (2.9 and 3.6 nmol substrate acetylated/mg protein/min) but neither had detectable NAT2 activity. Cells from both donors metabolized the pro-mutagens, although there were some significant differences in the extent of mutagenicity produced. HuPrEC(42) more efficiently converted the three heterocyclic amines to mutagens than the HuPrEC(17), the ratios being Glu-P-2 (2.3:1), MeIQx (1.6:1), and PhIP (7.3:1). These data show that human prostate epithelial cells can metabolize important dietary chemicals to mutagenic species.