Monitoring of mutagenic enhancers by use of the micronucleus test

我们接触到了环境中存在的许多化学物质。其中一些被称为诱变剂或致癌物。一项流行病学研究已经证明，肺癌的诱发与空气污染或吸烟之间存在相关性。然而，环境中存在的各种诱变剂或致癌物的含量太少，不足以诱发人类致癌。我们认为，研究这些化学物质的协同或相加效应以及环境中是否存在诱变或致癌促进剂是很重要的。本实验的目的是检测诱变剂的促进剂，并利用微核试验来证明增强剂的作用机制。BALB/c小鼠暴露于一氧化碳气体、缺氧空气或单纯钴暴露后，给予诱变剂后，其致突变活性(微核率)明显高于单独使用诱变剂。这个机制被认为是如下的。促红细胞生成素是哺乳动物红细胞形成的生理调节因子，可能是由于暴露在一氧化碳或氧气缺乏的空气中组织中的缺氧而诱导的。据报道，钴还能在哺乳动物体内诱导促红细胞生成素。加速骨髓中红细胞的分化和增殖过程，会增加DNA损伤的几率，从而增加微核的诱发率。我们部分地证明了这一机制，具体如下。促红细胞生成素可增加诱变剂诱发的微核率。前列腺素E_2增加肾促红细胞生成素，可增加诱变剂诱发的微核率。但是，吲哚美辛作为花生四烯酸级联反应的抑制剂，降低了诱变剂诱发的微核率。这些结果表明微核试验是检测环境中存在的诱变促进剂的有效方法。

We have been exposed to many chemicals existing in our environment. Some of them are known as mutagens or carcinogens. An epidemiological study have proved to be the correlation between an induction of lung cancer and air pollution or tobacco smoking. However, the content of each mutagen or carcinogen existed in our environment is too little to induce cancer for human. We considered it is important to study about the synergistic or additive effect of the chemicals and about the existence of mutagenic or carcinogenic enhancers in our environment.The aim of this experiment is to detect enhancers of mutagens, and to prove the mechanism of the enhancer by use of the micronucleus test. Mutagenic activity ( frequency of micronuclei ) was increased when mutagen was administered to BALB/c mice after the exposure to carbon monoxide gas, oxigen deficient air or cobalt compaired with mutagen alone. This mechanism is considered as follows. Erythropoietin, physiological regulator of red blood cell formation in mammals, might be induced due to an anoxia in tissue after exposure to carbon monoxide or oxigen deficient air. Cobalt has also reported to induce erythropoietin in mammals. Accelerating the differentiation and multiplication process of erythroblasts in bone marrow would increase the micronuclei induction because of the increased chance of DNA damage. We partly have proved this mechanisms as follows. Erythropoietin increased the frequency of micronuclei induced by mutagens. Prostaglandine E_2 which increase the renal erythropoietin increased the frequency of micronuclei induced by mutagens. But, indomethacin as an inhibitor of arachidonate cascade decreased the frequency of micronuclei induced by mutagens. These results suggest the micronucleus test is useful for detecting the mutagenic enhancers existing in environment.