Abstract
Continuous feeding of α-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 γ-glutamyl transpeptidase and α-fetoprotein. In liver, the increased γ-glutamyltranspeptidase and α-fetoprotein were predominantly confined to the proliferated ductular cell population. It is concluded that early stages of intoxication by the noncarcinogen α-naphthylisothiocyanate resemble early stages in induction of liver neoplasia by carcinogens that evoke ductular proliferation. Elevation of γ-glutamyltranspeptidase and α-fetoprotein expression by an expanding ductular cell population characterizes both processes. However, the increase is rapidly reversed after α-naphthylisothiocyanate is discontinued, in contrast to the persistence that has been reported when acetylaminofluorene was administered.
Supported in part by Grants CA-22484 and CA-07175 from the National Cancer Institute, NIH. A preliminary account of this work was presented at the 69th Annual Meeting of the American Association for Cancer Research (40).