Study on the Mechanism of Stress-caused Tumorigenesis and Its Nutritional Regulation

本研究旨在探讨应激诱发肿瘤发生的机制，并探索调控应激诱发肿瘤发生的营养方法。结果如下：（1）内源性组胺在肿瘤发生中的作用：组胺是肿瘤发生的关键物质之一。一般认为胺是由肥大细胞和嗜碱性粒细胞合成和释放的。还已知胺通过非肥大细胞中的组氨酸脱羧酶响应于有丝分裂原或肿瘤促进剂TPA而形成。然而，没有关于与酶诱导相关的细胞的信息。我们在这里首次表明，组氨酸脱羧酶在巨噬细胞中借助于从T淋巴细胞释放的可溶性因子而被诱导（报告1 - 7）。ii）抗坏血酸对组胺的去磷酸化作用：积累的证据表明抗坏血酸的抗肿瘤作用。接下来的研究是检查组胺和抗坏血酸对免疫反应的相互影响。结果表明，在小鼠淋巴细胞的胚细胞发生过程中，组胺通过培养物中的组氨酸脱羧酶形成，并且淋巴细胞转化被胺抑制。向培养物中加入抗坏血酸可引起内源性组胺的分解，从而解除组胺诱导的淋巴细胞胚细胞生成抑制（报告8、9）。

This study was carried out to investigate the mechanism of stress-induced tumorigenesis and to develop the nutritional methods for regulating the process. The results obtained are as follows:i) Role of endogenous histamine in tumorigenesis: Histamine is known as one of the key substances in development of tumors. It is generally accepted that the amine is synthesized and released from mast cells and basophils. It is also known that the amine is formed through histidine decarboxylase in non-mast cells in response to mitogens or tumor promotor, TPA. However, no information is available on cells which are associated with induction of the enzyme. We have shown here, for the first time, that histidine decarboxylase is induced in macrophages with the aid of soluble factor(s)released from T lymphocytes (reports 1 - 7).ii) Detoxification of histamine by ascorbic acid: Evidence is accumulated to indicate anti-tumor actions of ascorbic acid. The next study was to examine the mutual effects of histamine and ascorbic acid on immune reactions. The results obtained showed that during blastogenesis of mouse lymphocytes histamine was formed through histidine decarboxylase in the culture and that the lymphocyte transformation was suppressed by the amine. Addition of ascorbic acid to the culture caused decomposition of the endogenous histamine which led to derepression of the histamine-induced supression of the lymphocyte blastogenesis (reports 8,9).