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化学物质对无白蛋白血症大鼠和斯普拉格-道利大鼠肝脏癌前胎盘谷胱甘肽S-转移酶阳性病灶发育的修饰作用。

Modifying effects of chemicals on the development of liver preneoplastic placental glutathione S-transferase positive foci in analbuminemic and Sprague-Dawley rats.

作者信息

de Camargo J L, Tsuda H, Asamoto M, Tagawa Y, Wada S, Nagase S, Ito N

机构信息

First Department of Pathology, Nagoya City University Medical School, Japan.

出版信息

Toxicol Pathol. 1993;21(4):409-16. doi: 10.1177/019262339302100410.

DOI:10.1177/019262339302100410
PMID:8290874
Abstract

Nagase analbuminemic rats (NARs) were compared to the Sprague-Dawley (SD) stock in a medium-term assay system for hepatocarcinogenesis regarding their susceptibilities to the influence of chemicals on the development of glutathione S-transferase, placental form, positive (GST-P+) foci. Two weeks after initiation with diethylnitrosamine (DEN), the animals were exposed alternatively to 0.06% 3'-methyl-4-dimethyl-aminoazobenzene (3'-Me-DAB), 50 ppm DEN, 0.25% ethionine, 1% clofibrate, and 1% butylated hydroxyanisole (BHA) for a 6-wk period. Adequate controls included groups only initiated with DEN or treated with each test compound alone. For evaluation of the modifying potential of the chemicals, indices were generated by using the mean values obtained for number and area of GST-P+ foci after each treatment. Comparison between these indices suggests that SD rats were relatively more sensitive than NARs to the modifying effects of complete carcinogens (3'-Me-DAB and DEN). The strains were similarly-susceptible to the promoting influence of ethionine, a nongenotoxic carcinogen. The inhibitory influence of BHA was more intense in NARs, whereas in both strains clofibrate was associated to similarly reduced values for number and area of GST-P+ foci. The degree of susceptibility of each strain to the modifying influence of chemicals on foci development depended on the chemical agent investigated.

摘要

在一个用于肝癌发生的中期试验系统中,将长谷川无白蛋白血症大鼠(NARs)与斯普拉格-道利(SD)大鼠品系进行比较,观察它们对化学物质影响谷胱甘肽S-转移酶胎盘型阳性(GST-P+)灶发展的易感性。用二乙基亚硝胺(DEN)启动实验两周后,让动物交替接触0.06%的3'-甲基-4-二甲基氨基偶氮苯(3'-Me-DAB)、50 ppm的DEN、0.25%的乙硫氨酸、1%的氯贝丁酯和1%的丁基羟基茴香醚(BHA),为期6周。适当的对照组包括仅用DEN启动或单独用每种测试化合物处理的组。为了评估化学物质的修饰潜力,通过使用每次处理后GST-P+灶的数量和面积的平均值来生成指数。这些指数之间的比较表明,SD大鼠对完全致癌物(3'-Me-DAB和DEN)的修饰作用相对比NARs更敏感。这两个品系对非遗传毒性致癌物乙硫氨酸的促进作用同样敏感。BHA的抑制作用在NARs中更强,而在两个品系中,氯贝丁酯都与GST-P+灶数量和面积的类似降低值相关。每个品系对化学物质对灶发展的修饰影响的敏感程度取决于所研究的化学物质。

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