Effects of adenine and its isomer 4-aminopyrazolo-[3,4-d]-pyrimidine on 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced mortality in rats.

Adult male Fischer rats were given a single po dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equal to 2 times the LD50 to increase the serum and liver lipid concentrations and to induce mortality. In addition, animals were given 4-aminopyrazolo-[3,4-d]-pyrimidine (4APP), an agent that decreases serum lipids, or adenine (Ad), an agent that prevents the formation of fatty liver, to examine the relationship between changes in lipids and TCDD-induced mortality. The principal effect of 4APP on TCDD-induced mortality (325 micrograms TCDD/kg body wt) was that it shortened the mean time to death. In contrast, Ad stimulated feed consumption and decreased body weight loss, but the mean times to death were similar for TCDD and TCDD + Ad animals. Based on these mortality studies, 4APP, but not Ad, affects the TCDD-induced mortality in Fischer rats. The TCDD-induced sensitivity to 4APP, based on decreased mean time to death, implies that blocking the release and/or synthesis of triglyceride-rich lipoproteins by the liver, and the subsequent decrease in serum lipids, may play an important role in the TCDD-induced mortality. The increase in serum triglyceride associated with TCDD exposure appears to be essential in providing metabolic energy under circumstances where lipoprotein retrieval is reduced.