Persistently decreased hepatic levels of 5'-deoxy-5'-methylthioadenosine during regeneration of and chemical carcinogenesis in rat liver

The hepatic levels of 5'-deoxy-5'-methylthioadenosine (MTA) were measured in the livers of adult male Sprague-Dawley rats a) killed at various times during the liver regeneration process, b) killed at times after partial hepatectomy when the liver mass had already been completely restored (hereafter called post-regeneration livers), or c) continuously fed 3'-methyl-4-dimethyl-aminoazobenzene (CAS: 55-80-1) up to the full development of hepatoma and killed at regular intervals during hepatocarcinogenesis. Hepatic MTA levels were always significantly decreased, although to different degrees in both in vivo models of hepatic growth and at all times during the investigation. Astonishingly, the MTA levels were also significantly decreased in the post-regeneration livers, in which there was also a significant increase in the activity of adenosylmethionine decarboxylase (S-adenosyl-L-methionine decarboxylase; EC 4.1.1.50) with normal levels of activity of ornithine decarboxylase (EC 4.1.1.17). These results demonstrate that a) the MTA content is always decreased in rat liver whenever this organ is involved in a proliferative process (whether controlled or uncontrolled); b) the decrease in hepatic MTA content is a biochemical feature necessary for, but by no means by itself sufficient for, hepatocyte proliferation to occur, since this decrease remains long after complete restoration of the liver mass; and c) the return of the hepatocytes to the normal biochemical program after restoration of the liver mass is not complete, even though these cells become quiescent, because there are still some biochemical abnormalities in the post-regeneration livers.