Effects of the diazafluoranthen derivative AC-3579 (NSC-170561), a new experimental antitumour drug, on rat hepatoma.

Abstract

The effects of AC-3579 (NSC-170561), a new experimental antitumour drug which depresses phospholipid catabolism in liver, were compared in rat aflatoxin-induced hepatoma and in non-neoplastic hepatocytes surrounding the tumour. Ultrastructural lesions, characterized by the hypertrophy of the smooth endoplasmic reticulum and the presence of lamellate cytosomes appeared in both tissues. They were less marked in hepatoma than in non-neoplastic cells. As in control livers, they were related to an invrease in pohspholipid concentration due to the decrease of phospholipid breakdown. In addition, chemical analysis demonstrated differences between hepatoma, non-neoplastic aflatoxin-treated liver and control liver: total and free cholesterol were decreased, relative concentration of sphingomyelin increased and that of phosphatidylethanolamine decreased by about 50%, in both hepatoma and non-neoplastic liver. Phospholipid concentration was decreased by 50% in tumour cells. After AC-3579 treatment total cholesterol was increased 3.2 fold in non-neoplastic liver and 2.5 fold in hepatoma but not in control liver.