Effect of hypophysectomy and aflatoxin B1 on rat liver.

It has been reported that hypophysectomy protects against the hepatocarcinogenic action of aflatoxin B in rats. A study has been made of the effects of aflatoxin B, and hypophysectomy on the livers of rats of different ages. Four groups of animals have been used, weanlings, small and large hypophysectomized rats, and adult intact rats. Ingestion of 4 ppm aflatoxin B, for 4 to 5 weeks resulted in minimal changes in the livers of the weanlings and the hypophysectomized rats but caused massive necrosis in the livers of the adult intact animals. This was not related to the amount of diet consumed. The liver necrosis in the adult intact animals may have been due to the presence of a large tetraploid hepatocyte population. The absence of these cells could account for the resist ance of the weanlings. The considerable tetraploid hepa tocyte population present in the large hypophysectomized rats was not susceptible to the necrogenic action of the aflatoxin B, either fed or given as i.p. injections. Hepatic nucleic acid synthesis was reduced by hypophysectomy or the administration of aflatoxin B,. In both cases the effect was more marked in the tetraploid than in the diploid hepatocytes. Nucleic acid synthesis in the hypo physectomized rat was more resistant to inhibition by aflatoxin B, than that in intact rats. This appeared to be due to the lower basal level of nucleic acid synthesis in the hypophysectomized rat, the final inhibited levels being similar in the two groups of animals. The ability of the microsomal systems obtained from hypophysectomized rats to activate the aflatoxin B, did not appear to be significantly less than the ability of microsomes isolated from control rats. The possibility was raised that there is a close connec tion between the uptakes of aflatoxin B, and steroid hormones into the liver. These uptake mechanisms could be located primarily in the tetraploid hepatocytes. Hy pophysectomy could protect against the cytotoxic and carcinogenic actions of aflatoxin by removing the steroid uptake mechanism by which aflatoxin enters the subcel lular structures. The possible relationships between the cytotoxic and carcinogenic actions of aflatoxin are dis cussed.