Effect of aza-substituted nucleotides on the starve-refeed response of rats.

Rat liver glucose 6-phosphate dehydrogenase (G6PD) and malic enzyme (ME) activities were increased by starvation-refeeding to levels above those found in rats fed ad libitum. The increases in enzyme activities above ad libitum-fed levels were prevented by 8-azaguanine and 6-azauridine, but not by 2-azauridine. Blood insulin levels were not affected at the time studied. Two aza analogs, 8-azaadenine and 5-azacytidine, proved to be too toxic in this type of studies. Since 8-azahypoxanthine, 8-azaxanthine and 5-azauracil were neither effective in preventing the enzyme overshoot, nor toxic to the animals, it was concluded that the toxiciyty to the animals of 8-azaadenine and 5-azacytidine is due to the compounds themselves rather than to the breakdown products.