title: Early stimulation of polyamine biosynthesis during promotion by phenobarbital of diethylnitrosamine-induced rat liver carcinogenesis. The effects of variations of the S-adenosyl-L-methionine cellular pool.
abstract: A decrease of S-adenosyl-L-methionine liver content was observed between the 14th and the 35th day after the start of 2-acetylaminofluorene feeding in diethylnitrosamine-initiated rats according to the 'resistant-hepatocyte' model of hepatocarcinogenesis. The decrease was enhanced by phenobarbital given to the animals after the end of 2-acetylaminofluorene feeding. These changes were associated with an increase in ornithine decarboxylase activity and the spermidine:spermine ratio. S-adenosyl-L-methionine administration to rats caused a great fall in the percentage of gamma-glutamyltranspeptidase-positive liver as well as in polyamine synthesis. An increase in ornithine decarboxylase activity, associated with a decrease in the liver S-adenosyl-L-methionine pool, also occurred in normal animals on the first day following a partial hepatectomy and was enhanced by phenobarbital. The association of 2-acetylaminofluorene feeding with partial hepatectomy resulted in a slower liver regeneration, while the decrease in S-adenosyl-L-methionine level and the increase in polyamine synthesis were observed over a longer period of time after partial hepatectomy. These changes were further prolonged in diethylnitrosamine-initiated rats in which gamma-glutamyltranspeptidase-positive foci developed. In these animals a high level of polyamine synthesis was still present when liver regeneration was complete. At this stage of the observation period the labeling index was very low in surrounding liver, but still high in the gamma-glutamyltranspeptidase-positive areas. Phenobarbital stimulated polyamine synthesis and cell growth and further prolonged the period of time during which a high ornithine decarboxylase activity and labeling index were present. These results indicate that the liver lipotrope content could be a rate-limiting factor for cell growth and liver neoplasia promotion and this could depend on the modulation of polyamine biosynthesis.
authors.forename: F
authors.initials: F
authors.lastname: Feo
authors.forename: R
authors.initials: R
authors.lastname: Garcea
authors.forename: L
authors.initials: L
authors.lastname: Daino
authors.forename: R
authors.initials: R
authors.lastname: Pascale
authors.forename: L
authors.initials: L
authors.lastname: Pirisi
authors.forename: S
authors.initials: S
authors.lastname: Frassetto
authors.forename: M E
authors.initials: ME
authors.lastname: Ruggiu
mesh_terms: D015073:2-Acetylaminofluorene / Q000633:toxicity; D000818:Animals; D004052:Diethylnitrosamine / Q000633:toxicity*; D004790:Enzyme Induction; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008297:Male; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D010634:Phenobarbital / Q000633:toxicity*; D011073:Polyamines / Q000096:biosynthesis*; D011700:Putrescine / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D012436:S-Adenosylmethionine / Q000378:metabolism*; D013095:Spermidine / Q000096:biosynthesis; D013096:Spermine / Q000096:biosynthesis; D005723:gamma-Glutamyltransferase / Q000096:biosynthesis
chemical_list: D011073:Polyamines; D013096:Spermine; D004052:Diethylnitrosamine; D012436:S-Adenosylmethionine; D015073:2-Acetylaminofluorene; D005723:gamma-Glutamyltransferase; D009955:Ornithine Decarboxylase; D013095:Spermidine; D011700:Putrescine; D010634:Phenobarbital