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

最近的研究发现，在氨基酸和蛋白质的热解产物中存在一系列新的致突变和致癌杂环胺。其中一些已被证明存在于各种食品、香烟烟雾冷凝物、空气颗粒物和雨水中，它们被认为广泛分布于环境中，Trp-P-1和Trp-P-2最初是从色氨酸的热解产物中分离出来的，后来在熟食和香烟烟雾冷凝物中检测到。当饲喂该饲料时，Trp-P-1和T-P-2对小鼠和大鼠具有致癌作用。最近，我们的观察表明，Trp-P-1和Trp-P-2存在于尿毒症患者的透析液等人体样本中，以及白内障晶状体、尿液、胆汁和代谢器官中，表明人类实际上接触到了这些致癌物。Trp-P-1和Trp-P-2通过激活钙调蛋白-肌球蛋白轻链激酶引起血管平滑肌细胞收缩，通过阻断环氧合酶抑制人血小板TxB_2的产生，以及抑制PhA诱导的人淋巴细胞增殖。综上所述，这些观察表明Trp-P-1和Trp-P-2不仅具有致癌作用，而且具有细胞功能特异性作用。

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.