Cell transformation in vitro by food-derived heterocyclic amines Trp-P-1, Trp-P-2 and N-2-OH-PhIP

Citation
W. Pfau et H. Marquardt, Cell transformation in vitro by food-derived heterocyclic amines Trp-P-1, Trp-P-2 and N-2-OH-PhIP, TOXICOLOGY, 166(1-2), 2001, pp. 25-30
Citations number
26
Categorie Soggetti
Pharmacology & Toxicology
Journal title
TOXICOLOGY
ISSN journal
0300483X → ACNP
Volume
166
Issue
1-2
Year of publication
2001
Pages
25 - 30
Database
ISI
SICI code
0300-483X(20010914)166:1-2<25:CTIVBF>2.0.ZU;2-3
Abstract
Heterocyclic aromatic amines (HCA) are formed upon frying of poultry, fish or meat and have been shown to induce tumours in rodent bioassays. We inves tigated the transforming activity of HCA in an in vitro assay using the M2/ C3H mouse fibroblast cell line. An external metabolic activation system (ra t liver homogenate) was required in order to observe any HCA-induced cytoto xic effects or cell transforming activity. Trp-P-1 and Trp-P-2 are shown to be among the most potent transforming HCA that have been detected in food, Metabolic activation of HCA has been shown to proceed via N-hydroxylation of the exocyclic amino group. Therefore, we tested 2-hydroxyamino-1-methyl6 -phenylimidazo [4,5-b] pyridine (N-2-OH-PhIP) the activated metabolite of 2 -anino-1-methyl-6-phenylimidazo[4,5h]pyridine. N-2-OH-PhIP proved to be one of the most powerful compounds with transforming activity observable at a concentration as low as 30 nM. Since 2-amino-1-methyl-6-phenylimidazo[4,5-b ]pyridine (PhIP) is the most abundant HCA formed in fried and grilled food and N-hydroxylation appears to be the predominant pathway of human metaboli sm, these data support the hypothesis that HCA are involved in the aetiolog y of human cancer. (C) 2001 Elsevier Science Ireland Ltd. All rights reserv ed.