Further experiments on lipid peroxidation in transplanted and experimental hepatomas

• Published in: Toxicologic pathology Vol. 12; no. 2; p. 189
• Main Authors: Dianzani, M U, Canuto, R A, Rossi, M A, Poli, G, Garcea, R, Biocca, M E, Cecchini, G, Biasi, F, Ferro, M, Bassi, A M
• Format: Journal Article
• Language: English
• Published: United States 1984
• Subjects: Aminopyrine N-Demethylase - metabolism; Animals; Carcinogens - toxicity; Cytochrome P-450 Enzyme System - metabolism; Cytosol - enzymology; Diethylnitrosamine - toxicity; Disease Models, Animal; gamma-Glutamyltransferase - metabolism; Glutathione - metabolism; Glutathione Peroxidase - metabolism; Glutathione Reductase - metabolism; Glutathione Transferase - metabolism; Lipid Peroxidation - physiology; Liver Neoplasms, Experimental - chemically induced; Liver Neoplasms, Experimental - metabolism; Male; Microsomes, Liver - drug effects; Microsomes, Liver - enzymology; Neoplasm Transplantation; Precancerous Conditions - chemically induced; Precancerous Conditions - enzymology; Rats; Rats, Wistar; Tumor Cells, Cultured
• DOI: 10.1177/019262338401200213
• ISSN: 0192-6233

The results of experiments on the subject of lipid peroxidation in hepatomas are described. It is now clear that lipid peroxidation is strongly decreased in most highly dedifferentiated hepatomas. It seems evident that the extent of the decline is strictly related to the degree of dedifferentiation. The model of diethylnitrosamine carcinogenesis, according to the method by Solt, Medline and Farber, has been now adopted to study the stages of carcinogenesis. It was shown that a net decline in lipid peroxidation occurs as early as at the stage of reversible nodules and progresses until the development of clear hepatomas. This change is practically simultaneous with a decline in the efficiency of the enzymes of the drug metabolizing system and in the content of cytochrome P450-Glutathione content and metabolism show also important changes. In fact, a dramatic increase in gamma-glutamyl-transpeptidase takes place very early during carcinogenesis, and is responsible for large decline in total glutathione during incubation of the homogenates. Glutathione peroxidase activity, on the contrary, is decreased, whereas glutathione reductase does not show significant changes. The supernatant of highly anaplastic tumors inhibits lipid peroxidation in normal liver homogenates, suggesting the presence of substances provided with antioxidant properties. These cannot be, however, related to a higher glutathione content. Supernatants from early nodules seem to be unable to block lipid peroxidation in normal liver homogenates. Preliminary experiments done to study the aldehyde pattern produced during lipid peroxidation, both in hepatomas and in nodules, confirm the presence of very poor lipid peroxidation and possibly of different peroxidation kinetics.