Chloroform in Drinking Water Prevents Hepatic Cell Proliferation Induced by Chloroform Administered by Gavage in Corn Oil to Mice

Michael A. Pereira, Matthew Grothaus
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Abstract

Chloroform administered by gavage in corn oil, but not when administrated in drinking water, has been shown to induce liver cancer in female B6C3F1mice and to enhance cell proliferation. Since humans are exposed to chloroform in their drinking water, we evaluated whether exposure by this route would interact with the activity of chloroform when administered by gavage in corn oil. Female B6C3F1mice were exposed to chloroform in drinking water for 33 days at 0, 300, or 1800 ppm (Experiment 1) or for 31 days at 0, 120, 240, or 480 ppm (Experiment 2) and for 3 days prior to termination also received a daily dose of 263 mg/kg chloroform administered by gavage in corn oil. Exposure to chloroform in drinking water reduced both the hepatotoxicity and the enhanced cell proliferation (bromodeoxyuridine-labeling index and mitotic index) elicited in response to chloroform administered by gavage in corn oil. Hence, chloroform administered in drinking water reduced the activity of chloroform administered by gavage in corn oil, suggesting that it would also reduce the hepatocarcinogenic activity of chloroform administered by gavage.

饮水氯仿对玉米油灌胃氯仿诱导小鼠肝细胞增殖的抑制作用
在玉米油中灌胃氯仿,而不是在饮用水中灌胃氯仿,已被证明会诱发雌性b6c3f1小鼠的肝癌,并促进细胞增殖。由于人类在饮用水中接触到氯仿,我们评估了通过这种途径接触氯仿是否会与玉米油灌胃给药时氯仿的活性相互作用。雌性b6c3f1小鼠在饮用水中暴露于浓度为0、300或1800 ppm的氯仿33天(实验1),或暴露于浓度为0、120、240或480 ppm的氯仿31天(实验2),并在终止前3天以玉米油灌胃的方式每天给药263 mg/kg氯仿。暴露于饮用水中的氯仿降低了玉米油中氯仿灌胃引起的肝毒性和增强的细胞增殖(溴脱氧尿嘧啶标记指数和有丝分裂指数)。因此,饮用水中的氯仿降低了玉米油中灌胃给药的氯仿的活性,表明它也会降低灌胃给药的氯仿的肝癌活性。
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