Non-persisting early foci of altered hepatocytes induced in rats by N-nitrosomorpholine

Male Sprague-Dawley rats were treated for 7 weeks with 120 mg/l N-nitrosomorpholine in their drinking water. At the end of the treatment period there were large numbers of enzyme-altered foci in the liver. During the following 10 weeks, the number of foci decreased significantly. This decrease in the number of enzyme-altered foci was due to the disappearance of a special type of focus. The typical features of these non-persisting foci were distinct enzyme histochemical and striking morphological alterations as well as the localization in or close to the third zone, as defined by Rappaport. In contrast to the simultaneously appearing persisting foci, the non-persisting foci were always glycogen-poor or totally glycogen-free. Signs of cell death were frequently found in or near this type of focus. After these non-persisting foci had disappeared, the total number of pre-neoplastic lesions obviously remained constant. We conclude that this disappearance of early appearing, severely altered foci is due to cell loss caused by the non-specific toxic effect of the carcinogen.