phalloidine and Precancerous-Conditions

The phalloidin sensitivity of hepatocytes resulting in the formation of cytoplasmic blebs was examined with cells isolated from 73- to 74-week-old and 99- to 100-week-old F344/DuCrj rats of both sexes by a collagenase perfusion method. The cells isolated from aged rats were less sensitive to the toxin than those obtained from 10- to 14-week-old rats. The decrease in the sensitivity was more marked in males than in females, and it appeared at an earlier age in the former than in the latter. Phalloidin consumption experiments showed decreases in the cellular uptake of the toxin in aged rats, and these were more marked in males than in females. The low cellular uptake of the toxin seemed to play an important role in the low sensitivity of the cells in aged rats. Although histological and histochemical examinations showed the development of foci of altered hepatocytes in the aged rat liver, the foci were estimated to account for less than 1.5% of liver tissues. Thus, the decrease in the sensitivity of the cells isolated from whole liver tissues might mainly be attributed to the decrease in the sensitivity of otherwise normal-looking hepatocytes.

Topics: Aging; Animals; Female; gamma-Glutamyltransferase; Liver; Liver Neoplasms, Experimental; Male; Oligopeptides; Phalloidine; Precancerous Conditions; Rats; Rats, Inbred F344; Sex Factors

Male inbred F344 rats weighing about 150 g were fed continuously a diet containing 0.02% N-2-fluorenylacetamide for 14-15 weeks. The presumptively preneoplastic hepatocytes were transferred to an in vitro system after dispersion by a collagenase-perfusion technique. Sensitivity to phalloidin in terms of formation of cytoplasmic blebs on the cell surface was less in the presumptively preneoplastic hepatocytes than in normal hepatocytes. Among the presumptively preneoplastic hepatocytes, the gamma-glutamyltransferase (GGT)-positive cells were less sensitive to phalloidin than GGT-negative cells, indicating a greater contribution to the decrease in the sensitivity to phalloidin of the presumptively preneoplastic cells.

Topics: 2-Acetylaminofluorene; Animals; Drug Resistance; gamma-Glutamyltransferase; Histocytochemistry; In Vitro Techniques; Liver; Liver Neoplasms; Male; Neoplasms, Experimental; Oligopeptides; Phalloidine; Precancerous Conditions; Rats; Rats, Inbred F344