Further Experiments on Lipid Peroxidation in Transplanted and Experimental Hepatomas

Abstract

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.

Studies on the hyperplasia (‘regeneration’) of the rat liver following partial hepatectomy. Changes in lipid peroxidation and general biochemical aspects

“…Previous studies have shown that lipid peroxidation, a free-radical-mediated process, is generally greatly decreased in liver tumour cells and tumour cell fractions compared with corresponding samples of normal liver (Thiele & Huff, 1960;Utsumi et al, 1965;Fonnesu et al, 1966;Lash, 1966;Burlakova & Pal'mina, 1967;Ugazio et al, 1969;Burlakova, 1975;Bartoli & Galeotti, 1979;Player et al, 1979;Ahmed & Slater, 1981;Dianzani et al, 1984;Cheeseman et al, 1986aCheeseman et al, , 1988aMasotti et al, 1988). Detailed studies on the Novikoff (Cheeseman et al, 1986a) and Yoshida (Cheeseman et al, 1988a) tumours have identified an increased tumour cell content of c-tocopherol as a major contributory factor in the decreased rate of lipid peroxidation.…”

Studies on lipid peroxidation in normal and tumour tissues. The Yoshida rat liver tumour

“…One of the characteristic biochemical changes known to occur in rat liver tumours and in tumour fractions is a highly significant reduction in lipid peroxidation when exposed to pro-oxidant conditions compared with normal liver (Utsumi et al, 1965;Lash, 1966;Fonnesu et al, 1966;Ugazio et al, 1968;Burlakova, 1975;Gravela et al, 1975;Bartoli & Galeotti, 1979;Player et al, 1979;Dianzani et al, 1984;Sharma et al, 1984;Cheeseman et al, 1986a).…”

The chemopreventive effect of diallyl disulphide on N-nitrosodiethylamine induced heptocarcinogenesis

“…The level of lipid peroxidation products was found to be decreased in rat tumor cells and tissues when compared with the corresponding normal tissues (Dianzani et al 1984, Cheeseman et al 1986). Such a difference (Dianzani et al 1984, Cheeseman et al 1986) could be defined by (i) a decreased content of highly unsaturated fatty acids in tumors, (ii) a decreased concentration of cytochrome P-450 that can participate in the initiation of lipid peroxidation, (iii) a decreased content of NADPH content and (iv) changes in the antioxidant status and protective enzymes such as SOD and catalase. Experimental studies suggesting that lipid peroxidation has an inverse relationship with cell proliferation, corroborate our results (Nakagami, Uchida and Ohwada 1999).…”