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溴化和氯化乙腈的致突变性和致癌性评估:氯化副产物

Evaluation of mutagenic and carcinogenic properties of brominated and chlorinated acetonitriles: by-products of chlorination.

作者信息

Bull R J, Meier J R, Robinson M, Ringhand H P, Laurie R D, Stober J A

出版信息

Fundam Appl Toxicol. 1985 Dec;5(6 Pt 1):1065-74. doi: 10.1016/0272-0590(85)90142-3.

Abstract

The present study was undertaken to determine if chlorinated and brominated acetonitriles formed during the chlorination of drinking water possess mutagenic and/or carcinogenic properties. Chloroacetonitrile (CAN), dichloroacetonitrile (DCAN), trichloroacetonitrile (TCAN), bromochloroacetonitrile (BCAN), and dibromoacetonitrile (DBAN) were tested for their ability (1) to produce point mutations in the Salmonella/microsome assay, (2) to induce sister chromatid exchanges (SCE) in Chinese hamster ovary (CHO) cells in vitro, (3) to produce micronuclei in polychromatic erythrocytes in CD-1 mice, and (4) to act as tumor initiators in the skin of Sencar mice. DCAN and BCAN were found to be direct-acting mutagens in Salmonella. All five haloacetonitriles induced SCE in CHO cells in vitro. This activity paralleled the extent of chlorine substitution and was further enhanced in the dihaloacetonitrile series when bromine was substituted for chlorine. None of the haloacetonitriles showed evidence of activity in the mouse micronucleus assay. DBAN, BCAN, and CAN initiated tumors in the mouse skin with topical applications followed by a 20-week promotion schedule of 12-O tetradecanoylphorbol-13-acetate applications (p less than 0.02). These data indicate that the haloacetonitriles do display mutagenic and carcinogenic properties in some test systems and the hazard associated with their occurrence in drinking water and production within the gastrointestinal tract require further evaluation.

摘要

本研究旨在确定饮用水氯化过程中形成的氯化和溴化乙腈是否具有诱变和/或致癌特性。对氯乙腈(CAN)、二氯乙腈(DCAN)、三氯乙腈(TCAN)、溴氯乙腈(BCAN)和二溴乙腈(DBAN)进行了以下测试:(1)在沙门氏菌/微粒体试验中产生点突变的能力;(2)体外诱导中国仓鼠卵巢(CHO)细胞姐妹染色单体交换(SCE)的能力;(3)在CD-1小鼠的多色红细胞中产生微核的能力;(4)作为Sencar小鼠皮肤肿瘤启动剂的作用。发现DCAN和BCAN在沙门氏菌中是直接作用的诱变剂。所有五种卤代乙腈在体外CHO细胞中均诱导了SCE。这种活性与氯取代程度平行,并且在二卤代乙腈系列中,当用溴取代氯时进一步增强。没有一种卤代乙腈在小鼠微核试验中显示出活性证据。DBAN、BCAN和CAN通过局部应用,随后进行12-O-十四烷酰佛波醇-13-乙酸酯应用的20周促癌方案,在小鼠皮肤中引发了肿瘤(p<0.02)。这些数据表明,卤代乙腈在某些测试系统中确实表现出诱变和致癌特性,并且与它们在饮用水中的出现以及在胃肠道内产生相关的危害需要进一步评估。

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