Humans are exposed to numerous toxic compounds in foods. During the past decade, several carcinogenic heterocyclic amines have been reported to be present in the cooked foods. Recently, we reported that some of the carcinogenic heterocyclic amines isolated from foods were present in human plasma. In order to know the effects of the carcinogens isolated from foods on the cell function, we investigated the effects of the carcinogenic heterocyclic amines including Trp-P-1(3-amino-l,4-dimethyl-5H-pyrido❘4,3-b❘indole) and Trp-P-2(3-amino-1-methyl-5H-pyrido❘4,3-b❘indole) on human platelet aggregation and polymorphonuclear leukocyte aggregation. Only tryptophan pyrolysis products, Trp-P-1 and Trp-P-2, had potent inhibitory effects on human platelet aggregation when platelets were preincubated with the carcinogens for 15 min. Other carcinogenic heterocyclic amines such as glutamic acid pyrolysates (Glu-P-1 and Glu-P-2) and 3H-imidazo ❘4,5-f❘quinoline-2-amines(IQ and MelQ) did show no effect on platelet aggregation even at 100 μM.The autoradiogram demonstrated that Tryptophan pyrolysis products, Trp-P-1 and Trp-P-2, dose-dependently inhibited the formation of HHT,PGD2,PGE2 and TXB2 induced by sodium arachidonate in human platelets labeled with ❘ 14c❘ arachidonic acid. Moreover, Trp-P-1 and Trp-P-2 did not show significant effects on leukocyte aggregation induced by sodium arachidonate (0.75mM) even at lOOnM. It is concluded that Trp-P-1 and Trp-P-2 isolated from cooked foodstuffs have potent inhibitory effects on the cyclo-oxygenase pathway of the platelet. Therefore, human platelet function might be affected with daily foods containing tryptophan pyrolysis products in vivo.
Inhibition of agonist-induced platelet aggregation, Ca2+ mobilization and granule secretion by guanosine 5′-[β-thio]diphosphate and GDP in intact platelets. Evidence for an inhibitory mechanism unrelated to the inhibition of G-protein-GTP interaction
