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
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.