Experimental cancer studies of chlorinated by-products
Experimental cancer studies of chlorinated by-products
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DOI：
10.1016/j.tox.2004.01.031
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发表时间：
2004-05-20
期刊：
影响因子：
4.5
通讯作者：
Komulainen, H
中科院分区：
文献类型：
--
作者：
Komulainen, H
氯化饮用水含有在氯化过程中由有机物形成的许多不同的副产物。只有一小部分的致癌性在实验动物中得到了评估。重点是在氯化饮用水中含量最多的化合物和化合物组，或者体外毒性数据表明可能存在遗传毒性。从三卤甲烷中，氯仿引起小鼠和雌性大鼠的肝脏肿瘤和雄性小鼠和大鼠的肾脏肿瘤。氯仿的肿瘤形成与组织中的细胞毒性和再生细胞增殖密切相关，这被认为是其致癌性的一个决定因素。从卤代乙酸中，二氯乙酸（DCA）和三氯乙酸（TCA）对小鼠和雄性大鼠具有肝癌致癌性。它们的遗传毒性是模棱两可的，非遗传毒性机制，如过氧化物酶体增殖和肝脏DNA的低甲基化，可能有助于肿瘤的发展。来自氯化呋喃酮（CHFs）的3-氯-4-（二氯甲基）-5-羟基-2(5H)-呋喃酮（MX）是大鼠体内（如甲状腺和肝脏）的多位点致癌物，在体内引起DNA损伤。NIX可能是一种完全致癌物质，因为它在体外也具有启动子特性。如果原水含有溴化物，氯化饮用水也可能含有溴化副产品。其中至少有一些（溴二氯甲烷、溴仿）在实验动物中被证明具有致癌性。总的来说，虽然有几种副产品在实验动物身上被证明具有致癌潜力，但目前还不可能说明哪些化合物或副产品会导致氯化饮用水中的癌症风险。其作用的细胞机制和这些作用在低浓度下仍然知之甚少。对这些副产物混合的少数研究表明，混合效应可能是复杂和不可预测的（抑制性、加性、增效）。(C) 2004年由爱思唯尔爱尔兰有限公司出版
Chlorinated drinking water contains a number of different by-products formed during the chlorination process from organic matter. The carcinogenicity of only a fraction of them have been evaluated in experimental animals. The focus has been on compounds and groups of compounds that are most abundant in chlorinated drinking water or the in vitro toxicity data have suggested genotoxic potential. From trihalomethanes, chloroform causes liver tumors in mice and female rats and renal tumors in male mice and rats. Tumor formation by chloroform is strongly associated with cytotoxicity and regenerative cell proliferation in tissues and that has been considered to be one determinant of its carcinogenicity. From halogenic acetic acids, dichloroacetic acid (DCA) and trichlotoacetic acid (TCA) are hepatocarcinogenic in mice and DCA in male rats. Their genotoxicity is equivocal and nongenotoxic mechanisms, such as peroxisome proliferation and hypomethylation of DNA in the liver, likely contribute to tumor development. From chlorinated furanones (CHFs), 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) is a multisite carcinogen in rats (e.g. in thyroid glands and liver) and it has caused DNA damage in vivo. NIX may be a complete carcinogen because it also has promoter properties in vitro. Chlorinated drinking water may also contain brominated by-products providing the raw water contains bromide. At least some of them (bromodichloromethane, bromoform) have been shown to be carcinogenic in laboratory animals. Altogether, although several by-products have been shown to have carcinogenic potential in laboratory animals, it not yet possible to state which compounds or groups of by-products cause the cancer risk in chlorinated drinking water. The cellular mechanisms of their effects and these effects at low concentrations are still poorly understood. The few studies with mixtures of these by-products suggest that the mixture effects may be complex and unpredictable (inhibitory, additive, synergistic). (C) 2004 Published by Elsevier Ireland Ltd.