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

本研究旨在探讨应激诱导肿瘤形成的机制，并开发调节这一过程的营养方法。研究结果如下：1)内源性组胺在肿瘤发生中的作用：组胺被认为是肿瘤发生的关键物质之一。人们普遍认为，胺是由肥大细胞和嗜碱性粒细胞合成和释放的。也已知，胺是通过非肥大细胞中的组氨酸脱羧酶在有丝分裂原或肿瘤促进剂TPA的反应下形成的。然而，目前还没有与这种酶的诱导有关的细胞信息。我们在这里首次证明，在T淋巴细胞释放的可溶性因子(S)的帮助下，巨噬细胞中的组氨酸脱羧酶被诱导(报告1-7)。ii)抗坏血酸对组胺的解毒作用：有证据表明抗坏血酸具有抗肿瘤作用。下一项研究是研究组胺和抗坏血酸对免疫反应的相互影响。结果表明，在小鼠淋巴细胞转化过程中，培养物中的组氨酸脱羧酶生成组胺，抑制淋巴细胞转化。在培养中添加抗坏血酸会导致内源性组胺的分解，从而导致组胺诱导的淋巴细胞母细胞生成抑制的解除(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).