Synthesis and accumulation of polyamines in rat liver during chemical carcinogenesis

The activities of L-ornithine decarboxylase (EC 4.1.1.17) and S-adenosyl-L-methionine decarboxylase (EC 4.1.1.50) exhibited marked fluctuations in the livers of rats fed 4-dimethylaminoazobenzene. After 1 month of dye feeding the activity of ornithine decarboxylase rose to a level about 6 times higher than that of controls and the activity of adenosylmethionine decarboxylase was more than twice the initial control level. These elevations were transient and returned to near normal values within the next 2 mths. 4 mths after the commencement of the azo-dye diet, ornithine and adenosylmethionine decarboxylase activities showed a second distinct stimulation and appeared to remain high until liver tumors appeared. In contrast, the activity of tyrosine aminotransferase (EC 2.6.1.5) initially decreased but increased after 3 to 6 mths to levels slightly exceeding the control values. The biphasic response of the 2 decarboxylases to the carcinogen appeared to be specific for the liver since both enzyme activities showed a sharp decrease in the kidney during the first 3 mths of dye feeding followed by a transient increase 1 mth later. The concentration of putrescine in the liver roughly followed the fluctuation of ornithine decarboxylase activity, being about twice the control level in carcinogen treated rats. Spermidine and spermine concentrations were normal although the activities of spermidine synthase (EC 2.5.1.16) and spermine synthase appeared to be lower in animals fed the carcinogenic diet than in normal controls. The response of liver ornithine decarboxylase, adenosylmethionine decarboxylase and tyrosine aminotransferase to growth hormone, glucagon and hydrocortisone was measured several times during the course of the azo-dye diet. There were only small changes, if any, in the stimulation of tyrosine aminotransferase by growth hormone or hydrocortisone whereas the stimulation by glucagon was totally lost. The striking response of ornithine decarboxylase to porcine growth hormone was markedly reduced and the moderate stimulation elicited by glucagon completely disappeared during the carcinogenic diet. The response of adenosylmethionine decarboxylase to growth hormone remained unchanged, while the marginal stimulation evoked by either glucagen or hydrocortisone in normal rats totally disappeared after 4 mth of dye feeding. Elevated activities of ornithine decarboxylase and adenosylmethionine decarboxylase, together with a distinctly reduced response of these enzymes to hormonal stimulations, thus appear to be characteristics of rat liver undergoing chemical carcinogenesis