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 concentration^2–4, 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 methyltransferases^8,9, and so tRNA isolated from the liver of rats injected with adenine and ethionine is hypomethylated^10,11. It is well established that several eukaryotic mRNAs are methylated on the 5′ terminus and that such modification is essential for translation^12,13. 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 oviduct^14–17. 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 proteins^17,19. 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.