Influence of Hypophysectomy on the Biochemical Effects and Metabolism of Aflatoxin B1 in Rats

Summary

The influence of hypophysectomy in male rats on the inhibition of RNA synthesis in vivo by aflatoxin B1 and the metabolism of aflatoxin B1 by liver in vitro and in vivo was determined. RNA synthesis, as measured by the incorporation of 14C-orotic acid into the nucleic acid fraction of liver, was inhibited 46 and 65% by 0.33 and 0.50 mg aflatoxin/kg body weight, respectively, in intact rats. These levels of aflatoxin produced no significant inhibition in hypophysectomized rats. The metabolism of aflatoxin B by 9000Xg supernatants of liver homogenates, as measured by fluorescent-metabolite production in vitro, was altered by hypophysectomy. The production of aflatoxin M1, and one unidentified metabolite (X3) was not changed, but the metabolite X2 (produced primarily by the soluble, nonmicrosomal fraction of liver) was increased and metabolite X1 (produced by the microsomal fraction) markedly decreased. Hypophysectomy depressed the aminopyrine demethylase activity of these same liver preparations. Similar changes occurred when SKF 525-A (5X10-5 M) was added to the incubation system, except that aflatoxin M1 production was also slightly decreased. Aflatoxin B1 administered to rats intraperitoneally was cleared and/or metabolized by livers of intact rats faster than by those of hypophysectomized rats. These findings are discussed in relation to the reported resistance of hypophysectomized rats to the hepatocarcinogenic activity of aflatoxin.