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氯仿对B6C3F1小鼠致癌物诱导的胃肠道核异常的位点特异性调节。

Site-specific modulation of carcinogen-induced gastrointestinal tract nuclear anomalies in B6C3F1 mice by chloroform.

作者信息

Daniel F B, Reddy T V, Stober J A, Olson G R

机构信息

Health Effects Research Laboratory, U.S. Environmental Protection Agency, Cincinnati, OH 45268.

出版信息

Anticancer Res. 1991 Mar-Apr;11(2):665-70.

PMID:2064320
Abstract

Chloroform (CHCl3) is an established rodent carcinogen and a prevalent contaminant of chlorine-disinfected drinking water. Thus in the United States CHCl3, along with other trihalomethanes, is regulated not to exceed 100 ppb in potable water. Recently, several studies have shown that CHCl3 also has anti-cancer properties as it inhibits tumor growth in mouse liver and in the gastrointestinal tract of the rat. In this paper we show that CHCl3 also inhibits the propensity for three gastrointestinal tract carcinogens, benzo(a)pyrene (BAP), 1,2-dimethylhydrazine (DMH) and methylnitrosourea (MNU), to induce nuclear anomalies in the proximal colon of the B6C3F1 mouse. For example, in mice pre-adapted to 1800 ppm CHCl3 for 30 days prior to the carcinogen administration the level of nuclear anomalies induced in the proximal colon by BAP was reduced by four-fold (0.9 +/- 0.7 v. 3.6 +/- 1.0 anomalies/10 crypts; p less than 0.001) and two-fold for MNU (2.4 +/- 1.0 v. 4.6 +/- 1.6; p less than 0.001) and DMH (0.9 +/- 0.9 v. 1.7 +/- 0.8; p = 0.03). In the duodenum CHCl3 was effective at inhibiting unclear anomalies only for MNU (45.3 +/- 4.6 v. 30.4 +/- 3.5; p = 0.02). The inhibitory effect of CHCl3 does not extend to nuclear anomalies of the forestomach. The anti-cancer properties of CHCl3 are discussed in light of its cancer causing potential and possible application to human risk assessment.

摘要

氯仿(CHCl₃)是一种已被确认的啮齿动物致癌物,也是氯消毒饮用水中普遍存在的污染物。因此,在美国,氯仿与其他三卤甲烷一样,被规定在饮用水中的含量不得超过100 ppb(十亿分之一)。最近,多项研究表明,氯仿还具有抗癌特性,因为它能抑制小鼠肝脏和大鼠胃肠道中的肿瘤生长。在本文中,我们表明氯仿还能抑制三种胃肠道致癌物,即苯并(a)芘(BAP)、1,2 - 二甲基肼(DMH)和甲基亚硝基脲(MNU),在B6C3F1小鼠近端结肠中诱导核异常的倾向。例如,在给致癌物前预先适应1800 ppm氯仿30天的小鼠中,BAP在近端结肠中诱导的核异常水平降低了四倍(0.9 ± 0.7对3.6 ± 1.0个异常/10个隐窝;p < 0.001),MNU降低了两倍(2.4 ± 1.0对4.6 ± 1.6;p < 0.001),DMH降低了两倍(0.9 ± 0.9对1.7 ± 0.8;p = 0.03)。在十二指肠中,氯仿仅对MNU有效抑制核异常(45.3 ± 4.6对30.4 ± 3.5;p = 0.02)。氯仿的抑制作用并不延伸至前胃的核异常。根据氯仿的致癌潜力及其在人类风险评估中的可能应用,对其抗癌特性进行了讨论。

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