Dissimilar patterns of promotion by di(2-ethylhexyl)phthalate and phenobarbital of hepatocellular neoplasia initiated by diethylnitrosamine in B6C3F1 mice

作者：J M Ward, James Mahmud Rice, Donald A. Creasia, Peter Lynch, Charles Warburton Riggs · 发表于：Carcinogenesis · 年份：1983 · DOI：10.1093/carcin/4.8.1021 · 被引用次数：138 · 研究领域：Cancer-related Molecular Pathways、Carcinogens and Genotoxicity Assessment

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 simil...