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.
Lawson
Terence
T
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198-6805, USA. talawson@unmc.edu
Kolar
Carol
C
D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D001711:Biotransformation; D002460:Cell Line; D018920:Coculture Techniques; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics* / Q000494:pharmacology; D007527:Isoenzymes; D008297:Male; D009153:Mutagens / Q000378:metabolism* / Q000494:pharmacology; D011467:Prostate / Q000737:chemistry / Q000378:metabolism*; D011804:Quinolines / Q000493:pharmacokinetics*
D007093:Imidazoles; D007527:Isoenzymes; D009153:Mutagens; D011804:Quinolines; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D019388:Cytochrome P-450 CYP1A2; D000123:Acetyltransferases; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; C478900:NAT2 protein, human; D005982:Glutathione Transferase; C036989:2-amino-3,4-dimethylimidazo(4,5-f)quinoline; C023847:Glu-P-2