Effects of carcinogenic amino-gamma-carbolines on the cell toxicity

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Recent investigations have revealed a new series of mutagenic and carcinogenic heterocyclic amines in pyrolysates of amino acid and proteins. Some of them have been demonstrated to be present in various food stuffs, cigarette smoke condensate, airborne particles and rain water, and they are believed to be distributed widely in the environment Trp-P-1 and Trp-P-2 were originally isolated as potent mutagens from pyrolysates of tryptophan and subsequently detected in cooked foods and cigarette smoke condensate. When fed with the diet, Trp-P-1 and T-P-2 are carcinogenic to mice and rats. Recently, our observations showed that Trp-P-1 and Trp-P-2 were present in human samples such as dialysis fluid of patients with uremia, as well as in cataractous lenses, urine, bile and metabolic organs, indicating that humans are actually exposed to these carcinogens.In the present studies we examined the effects of carcinogenic Trp-P-1 and Trp-P-2 on the stimulus-reaction system in bovine vascular smooth muscle cells and human platelets and lymphocytes. Trp-P-1 and Trp-P-2 caused 1) the vascular smooth muscle cell constriction through the activation of calmodulin-myosin light chain kinase, 2) the inhibition of TxB_2 production in human platelets via the blockade of cyclooxygenase and 3) the inhibition of the human lymphocyte proliferation induced by PHA.Collectively, these observations indicate that Trp-P-1 ant Trp-P-2 have not only the carcinogenic effects but also the effects specific for cell functions.