In Vivo Studies On the Mechanism of Di(2-Ethylhexyl)Phthalate Carcinogenesis
In Vivo Studies On the Mechanism of Di(2-Ethylhexyl)Phthalate Carcinogenesis
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邻苯二甲酸二(2-乙基己基)酯致癌机制的体内研究
DOI：
10.1177/074823378700300211
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发表时间：
1987
影响因子：
1.9
通讯作者：
R. Cattley
中科院分区：
文献类型：
--
作者：
J. Popp;L. K. Garvey;R. Cattley
在一项由国家毒理学计划赞助的研究中，在饮食中添加1.2%的邻苯二甲酸二（2-乙基己基）（DEHP）显著增加了雌性大鼠患肝细胞癌的发病率。对DEHP致癌性的广泛评估得出了否定的结果。本研究旨在阐明DEHP在原始生物测定条件下的肝癌发生机制。短期研究旨在评估DEHP的促进能力，在启动后给药，当雌性fisher -344大鼠的肝脏使用多种组织化学染色评估以确定细胞改变灶时，结果为阴性。采用两种不同的方案，以组织化学定义的病灶为终点，评估DEHP在肝脏中的初始电位。两次实验的结果都是否定的。长期暴露于饮食中1.2%的DEHP 2年导致肝过氧化物酶体酶升高，而DNA复制（细胞增殖的一个指标）在肝细胞中不受影响。与对照组相比，DEHP组的病灶数量没有增加，尽管治疗组发生肝脏肿瘤的大鼠发生率较低。本系列的结果以及其他已发表的结果表明，DEHP和其他过氧化物酶体增殖化学物质对肝脏肿瘤的发展具有独特的作用。长期给药或起始-促进方案后没有病灶改变，将DEHP和其他过氧化物酶体增殖化学物质与经典的肝癌致癌物和促进物区分开来。
In a study sponsored by the National Toxicology Program, di(2-ethylhexyl)phthalate (DEHP) fed in the diet at 1.2% significantly increased the incidence of female rats with hepatocellular carcinomas. Extensive evaluation of DEHP for carcinogenicity has yielded negative results. The present investigations were designed to elucidate the mechanism of DEHP hepatocarcinogenesis under the conditions of the original bioassay. Short-term studies designed to evaluate the promoting capability of DEHP, when administered after initiation, were negative when livers of female Fischer-344 rats were evaluated using multiple histochemical stains to identify foci of cellular alteration. Two different protocols were used to evaluate the initiating potential of DEHP in the liver using histochemically defined foci as the endpoint. In both experiments the results were negative. Chronic exposure to DEHP at 1.2% in the diet for 2 years resulted in elevation of hepatic peroxisomal enzymes while DNA replication, an indication of cell proliferation, was not affected in hepatocytes. The number of foci was not elevated in the DEHP group compared to the controls, even though a low incidence of rats with liver tumors occurred in the treated group. The results of this series, as well as other published results, suggest that DEHP and other peroxisomal proliferating chemicals have unique effects on the development of hepatic neoplasms. The absence of altered foci after chronic administration or in initiation-promotion protocols distinguishes DEHP and perhaps other peroxisomal proliferating chemicals from both classic liver carcinogens and promoters.
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雄性 B6C3F1 小鼠短期暴露后，邻苯二甲酸二（2-乙基己基）酯而非苯巴比妥会促进 N-亚硝基二乙胺引发的肝细胞增殖性病变。
影响因子：
9.7
作者：
Ward,JM;Ohshima,M;Lynch,P;Riggs,C
通讯作者：
Riggs,C
抑制喂食弱致癌环境污染物的大鼠肝脏中癌前病变的发展。
影响因子：
9.7
作者：
Deangelo,AB;Garrett,CT
通讯作者：
Garrett,CT
邻苯二甲酸二(2-乙基己基)酯在体内和体外的肿瘤引发和促进活性。
影响因子：
10.4
作者：
Ward,JM;Diwan,BA;Ohshima,M;Hu,H;Schuller,HM;Rice,JM
通讯作者：
Rice,JM
通过单独给予降血脂过氧化物酶体增殖剂或单剂量二乙基亚硝胺后诱导大鼠肝病灶改变。
影响因子：
11.2
作者：
Glauert,HP;Beer,D;Rao,MS;Schwarz,M;Xu,YD;Goldsworthy,TL;Coloma,J;Pitot,HC
通讯作者：
Pitot,HC
邻苯二甲酸二(2-乙基己基)酯和苯巴比妥对 B6C3F1 小鼠中二乙基亚硝胺引发的肝细胞肿瘤的促进作用不同。
影响因子：
4.7
作者：
Ward,JM;Rice,JM;Creasia,D;Lynch,P;Riggs,C
通讯作者：
Riggs,C