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首页> 外文期刊>Journal of applied toxicology >Investigation of potential early key events and mode of action for 1,2-dichloroethane-induced mammary tumors in female rats
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Investigation of potential early key events and mode of action for 1,2-dichloroethane-induced mammary tumors in female rats

机译：雌性大鼠1,2-二氯乙烷诱导的乳腺癌潜在早期关键事件及其作用方式

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1,2-dichloroethane (DCE or EDC) is a chlorinated hydrocarbon used as a chemical intermediate, including in the synthesis of polyvinyl chloride. Although DCE has induced tumors in both rats and mice, the overall weight-of-evidence suggests a lack of in vivo mutagenicity. The present study was conducted to explore a potential mode of action further for tumor formation in rat mammary tissue. Fischer 344 rats were exposed to target concentrations of 0 or 200 ppm of DCE vapors (6 hours/day, 7 days/week) for at least 28 days; 200 ppm represents a concentration of similar to 20% higher than that reported to induce mammary tumors. Endpoints examined included DNA damage (via Comet assay), glutathione (reduced, oxidized and conjugated), tissue DNA adducts, cell proliferation and serum prolactin levels. Exposure to DCE did not alter serum prolactin levels with consistent estrous stage, did not cause cell proliferation in mammary epithelial cells, nor result in histopathological alterations in the mammary gland. DNA adducts were identified, including the N-7-guanylethyl glutathione adduct, with higher adduct levels measured in liver (nontumorigenic target) compared with mammary tissue isolated from the same rats; no known mutagenic adducts were identified. DCE did not increase the Comet assay response in mammary epithelial cells, whereas DNA damage in the positive control (N-nitroso-N-methylurea) was significantly increased. Although the result of this study did not identify a specific mode of action for DCE-induced mammary tumors in rats, the lack of any exposure-related genotoxic responses further contributes to the weight-of-evidence suggesting that DCE is a nongenotoxic carcinogen.
机译：1,2-二氯乙烷（DCE或EDC）是一种氯代烃，用作化学中间体，包括合成聚氯乙烯。尽管DCE已在大鼠和小鼠中诱发肿瘤，但总体证据表明缺乏体内致突变性。本研究旨在进一步探索大鼠乳腺组织中肿瘤形成的潜在作用模式。将Fischer 344只大鼠暴露于0或200 ppm DCE蒸汽的目标浓度（6小时/天，7天/周）至少28天；200 ppm的浓度比据报道的诱发乳腺肿瘤的浓度高20%。检测终点包括DNA损伤（通过彗星试验）、谷胱甘肽（还原、氧化和结合）、组织DNA加合物、细胞增殖和血清催乳素水平。暴露于DCE不会改变持续发情期的血清催乳素水平，不会导致乳腺上皮细胞增殖，也不会导致乳腺组织病理学改变。DNA加合物被鉴定，包括N-7-鸟苷乙基谷胱甘肽加合物，与从相同大鼠分离的乳腺组织相比，在肝脏（非肿瘤靶点）中测得的加合物水平更高；未发现已知的诱变加合物。DCE没有增加乳腺上皮细胞的彗星试验反应，而阳性对照组（N-亚硝基-N-甲基脲）的DNA损伤显著增加。虽然这项研究的结果没有确定DCE诱导的大鼠乳腺肿瘤的具体作用模式，但缺乏任何与暴露相关的基因毒性反应进一步增加了证据的份量，表明DCE是一种非基因毒性致癌物。

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