Gans J H, Pintauro S J
Proc Soc Exp Biol Med. 1986 Nov;183(2):207-13. doi: 10.3181/00379727-183-42406.
Exposure of mice for 8 weeks to drinking water containing diethylnitrosamine (DEN) was accompanied by alterations in hepatocyte structure and varying degrees of liver nonparenchymal cell (NPC) proliferation. Eighteen and a half weeks after cessation of DEN exposure, there was a 47% incidence of hepatocellular nodules. Centrilobular hepatocyte hypertrophy occurred consistently in mice given intraperitoneal injections of the polychlorinated biphenyl (PCB) mixture Aroclor 1254. PCB administration to mice previously treated with DEN was not accompanied by increases in gross liver nodule incidence above that induced by DEN, but many more developing microscopic nodules within the liver were observed in DEN-treated mice given Aroclor 1254 than in mice treated only with DEN. Aroclor 1254 administration over a 16-week period to mice previously treated with DEN was accompanied by an 83% incidence of severe distortion of liver structure resulting from nodule formation, uneven patterns of hepatocyte growth, and extensive deposition of scar tissue containing proliferating bile ducts. Morphological evidence of intestinal metaplasia was observed in proliferating bile duct-like structures during an early stage of liver adenofibrosis.
将小鼠暴露于含二乙基亚硝胺（DEN）的饮用水中8周，会伴随肝细胞结构改变以及不同程度的肝脏非实质细胞（NPC）增殖。停止DEN暴露18.5周后，肝细胞结节的发生率为47%。给小鼠腹腔注射多氯联苯（PCB）混合物Aroclor 1254后，始终会出现中央小叶肝细胞肥大。给先前用DEN处理过的小鼠施用PCB后，肝脏肉眼可见结节的发生率并未高于DEN诱导的发生率，但与仅用DEN处理的小鼠相比，在接受Aroclor 1254处理的DEN处理小鼠肝脏中观察到更多正在形成的微小结节。在先前用DEN处理过的小鼠中，连续16周施用Aroclor 1254，83%的小鼠出现因结节形成、肝细胞生长模式不均以及含有增殖胆管的瘢痕组织广泛沉积导致的肝脏结构严重变形。在肝腺纤维化早期，在增殖的胆管样结构中观察到肠化生的形态学证据。
