Induction of ovalbumin and conalbumin synthesis in immature chick oviducts by ethionine.

Abstract

PROLONGED feeding of rats with ethionine results in a high frequency of hepatic carcinoma. Ethionine induces other pathological manifestations in other organs and tissues of experimental animals1, and some of its effects can be reversed rapidly by the administration of methionine. At the molecular level ethionine induces a rapid decrease in hepatic ATP concentration2–4, followed by inhibition of RNA5 and protein synthesis6. The decrease in ATP concentration is due to formation of S-adenosyl-ethionine7, an inhibitor of tRNA methyltransferases8,9, and so tRNA isolated from the liver of rats injected with adenine and ethionine is hypomethylated10,11. It is well established that several eukaryotic mRNAs are methylated on the 5′ terminus and that such modification is essential for translation12,13. To study the mechanism of methylation we attempted to produce a specific methyl-deficient mRNA by the administration of ethionine. To monitor the effectiveness of the deprivation of methyl groups the synthesis of hormone-induced ovalbumin in immature chick oviducts was followed. Administration of oestrogen to immature chicks causes cytodifferentiation and growth of the primitive oviduct14–17. The tubular gland cells synthesise ovalbumin, conalbumin, ovomucoid and lysozyme which comprise 85–90% of the egg-white proteins18. The continuous presence of oestrogen is required for sustained synthesis of these proteins in immature chicks; withdrawal of oestrogen is accompanied by a gradual decline in cell-specific protein synthesis as well as in the weight of the oviduct and the RNA content of the tissue17. But, the tubular gland cells in the oviduct magnum during withdrawal are retained although they do not synthesise cell-specific secretory proteins17,19. Readministration of hormone to chicks after withdrawal (secondary stimulation) results in restoration of cell-specific protein synthesis without concomitant need for DNA synthesis17. During these studies ethionine unexpectedly simulated the effects of the injection of oestrogen for secondary stimulation.