Richards W L, Tsukada Y, Potter V R
Cancer Res. 1982 Dec;42(12):5133-8.
Continuous feeding of alpha-naphthylisothiocyanate to young male Sprague-Dawley rats was shown to produce a concentration-dependent increase in the number of hepatic ductular cells and a concentration- and time-dependent elevation of serum and liver gamma-glutamyl transpeptidase and alpha-fetoprotein. In liver, the increased gamma-glutamyltranspeptidase and alpha-fetoprotein were predominantly confined to the proliferative ductular cell population. It is concluded that early stages of intoxication by the noncarcinogen alpha-naphthylisothiocyanate resemble early stages in induction of liver neoplasia by carcinogens that evoke ductular proliferation. Elevation of gamma-glutamyltranspeptidase and alpha-fetoprotein expression by an expanding ductular cell population characterizes both processes. However, the increase is rapidly reversed after alpha-naphthylisothiocyanate is discontinued, in contrast to the persistence that has been reported when acetylaminofluorene was administered.
研究表明，持续给幼年雄性斯普拉格-道利大鼠喂食α-萘基异硫氰酸盐会导致肝内小胆管细胞数量呈浓度依赖性增加，血清和肝脏γ-谷氨酰转肽酶以及甲胎蛋白水平呈浓度和时间依赖性升高。在肝脏中，γ-谷氨酰转肽酶和甲胎蛋白的增加主要局限于增殖的小胆管细胞群体。得出的结论是，非致癌物α-萘基异硫氰酸盐中毒的早期阶段类似于引发小胆管增殖的致癌物诱导肝脏肿瘤形成的早期阶段。小胆管细胞群体扩张导致γ-谷氨酰转肽酶和甲胎蛋白表达升高是这两个过程的特征。然而，与给予乙酰氨基芴时所报道的持续情况相反，停用α-萘基异硫氰酸盐后这种增加会迅速逆转。
