Dissimilar patterns of promotion by di(2-ethylhexyl)phthalate and phenobarbital of hepatocellular neoplasia initiated by diethylnitrosamine in B6C3F1 mice.
Dissimilar patterns of promotion by di(2-ethylhexyl)phthalate and phenobarbital of hepatocellular neoplasia initiated by diethylnitrosamine in B6C3F1 mice.
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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。
DOI：
10.1093/carcin/4.8.1021
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发表时间：
1983
期刊：
影响因子：
4.7
通讯作者：
Riggs,C
中科院分区：
文献类型：
--
作者：
Ward,JM;Rice,JM;Creasia,D;Lynch,P;Riggs,C
在断奶雄性B6C3F1小鼠中，研究了潜在的肿瘤前肝细胞增生灶和肝细胞肿瘤，这些小鼠在4周龄时接受单次腹腔注射（80 mg/kg）二乙基亚硝胺（DEN），然后在DEN注射后2周开始口服苯巴比妥（PB）或二（2-乙基己基）邻苯二甲酸酯（DEHP），持续6个月。在饮用水中分别于下午500点给予PB，在饲料中分别于下午3000、6000和12000点给予DEHP。在DEN暴露后2、4和6个月处死各组小鼠；对经福尔马林固定的肝脏标本进行组织学评价。利用图像分析计算机对肝细胞肿瘤和增生灶进行定量分析。单独暴露于DEN、PB或DEHP的小鼠在2、4或6个月时很少见灶，而在DEN后暴露于DEHP或PB的小鼠中可见大量灶和肿瘤。每个肝细胞病灶或肿瘤横断的面积周长测量显示，在整个研究过程中，pb暴露小鼠的病灶和肿瘤的大小（面积和体积）和数量都增加了。在dehp暴露的小鼠中，反应模式有所不同，在4至6个月期间，病灶数量没有增加，但在整个实验过程中，病灶的平均直径和体积都有所增加。饮食中DEHP含量较高的小鼠比饮食中DEHP含量较低的小鼠更早出现病灶和肿瘤。在研究结束时，给予任何剂量DEHP的小鼠，每单位体积肝脏的病灶数量是相似的，但它们的体积是剂量相关的。pb暴露小鼠的肝细胞灶和肿瘤主要由嗜酸性肝细胞组成，而DEHP暴露小鼠的肝细胞灶和肿瘤以嗜碱性肝细胞为主；后者在外观上比暴露于pb小鼠的肿瘤更恶性。在6个月时，高剂量dehp暴露小鼠的肿瘤明显大于PB暴露小鼠。然而，组织化学揭示了暴露于PB或DEHP的小鼠的病变之间的相似性。连续给予PB 6个月后，1次灌胃和随后饮水给予PB均无DEHP启动活性。小鼠在一次暴露于具有起始活性的致癌物后发生的肝细胞灶和肿瘤的形态学和生物学，因此在一定程度上取决于随后的促进剂。在小鼠肝周期中，以特定的形态和生化变化序列为特征的不止一种肿瘤促进过程是可能的。
Potentially preneoplastic hepatocellular hyperplastic foci and hepatocellular neoplasms were studied in weanling male B6C3F1 mice that received a single i.p. injection (80 mg/kg) of diethylnitrosamine (DEN) at 4 weeks of age, followed by oral administration of phenobarbital (PB) or di(2-ethylhexyl)- phthalate (DEHP) that began 2 weeks after DEN injection and continued for up to 6 months. PB was administered in drinking water at 500 p.p.m. and DEHP in the feed at 3000, 6000 or 12 000 p.p.m. Groups of mice were sacrificed at 2, 4 and 6 months after DEN exposure; formalin-fixed liver samples were evaluated histologically. Hepatocellular neoplasms and foci of hyperplasia were quantified with the aid of an image analysis computer. Few foci were seen at 2, 4 or 6 months in mice exposed to DEN, PB or DEHP alone, while numerous foci and neoplasms were seen in mice given DEHP or PB after DEN. Area-perimeter measurements for each hepatocellular focus or neoplasm transection revealed that foci and neoplasms in PB-exposed mice increased both in size (area and volume) and in number throughout the study. In DEHP-exposed mice the pattern of response was different in that the numbers of foci did not increase between 4 and 6 months, but the foci increased in mean diameter and volume throughout the experiment. Foci and tumors appeared earlier in mice given higher dietary levels of DEHP than in those given lower doses. By the end of the study the number of foci per unit volume of liver was similar in mice given any dose of DEHP, but their volume was dose-related. Hepatocellular foci and neoplasms in PB-exposed mice were composed predominantly of eosinophilic hepatocytes, while in DEHP exposed mice, basophilic foci and neoplasms predominated; the latter were more malignant in appearance than neoplasms in PB-exposed mice. At 6 months, the neoplasms in high dose DEHP-exposed mice were significantly larger than those in PB exposed mice. Histochemistry, however, revealed similarities between lesions in mice exposed to PB or DEHP. PB given continuously for 6 months revealed no initiating activity of DEHP given once by gavage and followed by PB in drinking water. Both morphology and biology of hepatocellular foci and neoplasms, which develop in mice after a single exposure to a carcinogen with initiating activity, thus depend, in part, on the subsequent promoting agent. More than one process of tumor promotion, as characterized by a specific sequence of morphologic and biochemical changes, is possible for the mouse hepatocyle.