MORPHOMETRIC STUDY OF ALTERATIONS OF EXTRAFOCAL HEPATOCYTES OF RAT-LIVER TREATED WITH N-NITROSOMORPHOLINE

Male Sprague-Dawley rats were treated with the hepatocarcinogen N-nitrosomorpholine for 7 weeks and observed for up to 40 weeks after withdrawal of the carcinogen. In addition to the focal preneoplastic lesions described earlier there were also alterations in extrafocal hepatocytes and these changes have been quantified morphometrically. Since the periportal and perivenous hepatocytes were not altered to the same extent, cells of the periportal zone (PPZ) and cells of the perivenous zone (PVZ) were measured separately. Immediately after stopping treatment there was marked enlargement of the hepatocellular cytoplasm and of the nuclei in both the PPZ and the PVZ and a reduction in the number of binuclear hepatocytes. While these alterations were totally reversed during the first 10 weeks after treatment ceased in the PPZ, statistically significant changes in nuclear size, nuclear-cytoplasmic ratio and number of binuclear cells persisted in the PVZ up to 40 weeks after the end of treatment. We suggest that both the foci of altered hepatocytes as well as the persisting changes in extrafocal hepatocytes may be involved in the process of hepatocarcinogenesis.