Human prostate epithelial cells metabolize chemicals of dietary origin to mutagens

Terence Lawson, Carol Kolar

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Human prostate epithelial cells from a 17- and 42-year-old donor and designated as HuPrEC17 and HuPrEC42, 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. HUPrEC17 expressed a slow form of NAT1 (*4/*3) and an intermediate form of NAT2 (*4/*6) while HuPrEC42 expressed the rapid form of NAT1 (*10/*10) and an intermediate form of NAT2 (*4/*5). Both had comparable NAT1 activity (2.9 and 3.6nmol 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. HuPrEC42 more efficiently converted the three heterocyclic amines to mutagens than the HuPrEC17, 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.

Original languageEnglish (US)
Pages (from-to)141-146
Number of pages6
JournalCancer Letters
Volume175
Issue number2
DOIs
StatePublished - Jan 25 2002

Fingerprint

Mutagens
Prostate
Epithelial Cells
Genotype
Arylamine N-Acetyltransferase
Mutagenicity Tests
Quinoxalines
Cytochromes
Glutathione Transferase
Amines
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
Glu-P-2
Proteins

Keywords

  • Arylamine N-acetyltransferase
  • Glutathione S-transferase
  • Heterocyclic amine
  • Human
  • Mutagenicity
  • Prostate

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Human prostate epithelial cells metabolize chemicals of dietary origin to mutagens. / Lawson, Terence; Kolar, Carol.

In: Cancer Letters, Vol. 175, No. 2, 25.01.2002, p. 141-146.

Research output: Contribution to journalArticle

Lawson, Terence ; Kolar, Carol. / Human prostate epithelial cells metabolize chemicals of dietary origin to mutagens. In: Cancer Letters. 2002 ; Vol. 175, No. 2. pp. 141-146.
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abstract = "Human prostate epithelial cells from a 17- and 42-year-old donor and designated as HuPrEC17 and HuPrEC42, 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. HUPrEC17 expressed a slow form of NAT1 (*4/*3) and an intermediate form of NAT2 (*4/*6) while HuPrEC42 expressed the rapid form of NAT1 (*10/*10) and an intermediate form of NAT2 (*4/*5). Both had comparable NAT1 activity (2.9 and 3.6nmol 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. HuPrEC42 more efficiently converted the three heterocyclic amines to mutagens than the HuPrEC17, 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.",
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