Liver cancer is induced by a subnecrogenic dose of DENA when associated with fasting/refeeding: role of glutathione-transferase and lipid peroxidation.
In previous studies, we reported that fasting/refeeding has a role in sustaining the initiation of liver cancer by a subnecrogenic (noninitiating) dose of diethylnitrosamine (DENA). This research investigated whether the metabolic alterations imposed by fasting/refeeding provide an imbalance between the generation of carcinogenic molecules and the scavenger defense mechanisms in rat liver. Metabolism of DENA, levels of reduced glutathione (GSH) and GSH transferase (GST) activity, as well as basal and stimulated malondialdehyde (MDA) production, were examined. Rats fasted for 4 days showed a decrease in the liver levels of GSH, GST activity, monounsaturated fatty acids and % of labeled nuclei. After 1 day of refeeding, at which point DENA was administered, the levels of GSH recovered, GST activity remained below control values, basal and stimulated MDA production and content of total polyunsaturated fatty acids in liver phospholipids decreased. One day after DENA treatment, MDA production further decreased, although the % of labeled nuclei increased. No significant changes in the content of arachidonic acid, the main target of peroxidation, were observed at any time. The results indicated that the induction of the hepatocellular carcinoma was associated with a depression of GST activity and lipid peroxidation when rats were given 20 mg/kg of DENA after 1 day of refeeding after 4-day fasting.
Muzio
G
G
Dipartimento di Medicina e Oncologia Sperimentale, Universita' di Torino, Italy.
Marengo
B
B
Salvo
R
R
Semeraro
A
A
Canuto
R A
RA
Tessitore
L
L
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D003043:Cocarcinogenesis; D004052:Diethylnitrosamine / Q000008:administration & dosage / Q000633:toxicity*; D004435:Eating; D005215:Fasting; D005227:Fatty Acids / Q000032:analysis; D016166:Free Radical Scavengers / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000209:etiology* / Q000378:metabolism*; D008297:Male; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D000975:Antioxidants; D002273:Carcinogens; D005227:Fatty Acids; D016166:Free Radical Scavengers; D005609:Free Radicals; D010743:Phospholipids; D004052:Diethylnitrosamine; D005982:Glutathione Transferase; D005978:Glutathione