Ghanayem B I, Maronpot R R, Matthews H B
Cancer Lett. 1986 Sep;32(3):271-8. doi: 10.1016/0304-3835(86)90179-5.
A number of chemicals have been shown to cause malignant neoplasms in the forestomach of Fischer 344 rats when administered chronically by gavage. The present study was designed to identify early forestomach lesions following 2-week repeated gavage administration of some of these forestomach carcinogens. In this manner, we attempted to examine the hypothesis that early cell proliferation is associated with repetitive gavage administration of these chemicals. Groups of 8 or more male F344 rats received 1 of 6 reported forestomach carcinogens (ethyl acrylate (EtAc), diglycidyl resorcinol ether(DGRE), 1,2-dibromoethane (DBE), 1,2-dibromo-3-chloro-propane (DBCP), 1-chloro-2-methylpropene (dimethylvinyl chloride, DMVC) and 3-chloro-2-methylpropene (CMP)), 1 of 2 structurally related chemicals (methyl methacrylate (MMA) and dichloroethane (DCE)) which were negative in chronic carcinogenicity studies or the vehicle (corn oil) alone 5 days/week for 2 weeks. Histopathologic examination of forestomachs of rats killed 24 h after the last dose indicated no significant difference in the incidence or severity of epithelial cell proliferation in the rat forestomach between the vehicle control group and the 2 negative control groups. In contrast, the incidence and severity of epithelial cell proliferation of the rat forestomach in every group treated with a forestomach carcinogen was significantly higher than the incidence in the vehicle or negative control groups. These results suggest that early epithelial cell proliferation of the forestomach may be associated with at least some chemicals that induce forestomach neoplasia following chronic administration by gavage.
当通过灌胃长期给予时，多种化学物质已被证明可在Fischer 344大鼠的前胃中引发恶性肿瘤。本研究旨在确定在对其中一些前胃癌致癌物进行为期2周的重复灌胃给药后早期的前胃病变。通过这种方式，我们试图检验早期细胞增殖与这些化学物质的重复灌胃给药相关的假设。每组8只或更多只雄性F344大鼠接受6种已报道的前胃癌致癌物（丙烯酸乙酯（EtAc）、间苯二酚二缩水甘油醚（DGRE）、1,2 - 二溴乙烷（DBE））中的一种、1,2 - 二溴 - 3 - 氯丙烷（DBCP）、1 - 氯 - 2 - 甲基丙烯（二甲基氯乙烯，DMVC）和3 - 氯 - 2 - 甲基丙烯（CMP））、2种结构相关的化学物质（甲基丙烯酸甲酯（MMA）和二氯乙烷（DCE），它们在慢性致癌性研究中呈阴性）中的一种或仅接受赋形剂（玉米油），每周给药5天，持续2周。对在最后一剂后24小时处死的大鼠的前胃进行组织病理学检查表明，赋形剂对照组和两个阴性对照组之间大鼠前胃上皮细胞增殖的发生率或严重程度没有显著差异。相比之下，用前胃癌致癌物处理的每组大鼠前胃上皮细胞增殖的发生率和严重程度均显著高于赋形剂或阴性对照组。这些结果表明，前胃的早期上皮细胞增殖可能与至少一些通过灌胃长期给药后诱导前胃肿瘤形成的化学物质有关。
