DL-Ethionine, an antagonist of Methionine, is toxic and a carcinogen [1]. DL-Ethionine could increase the cyclic AMP content and stimulate the malignant transformation of cells [2]. DL-Ethionine has been widely used to induce hepatocarcinogenesis in rats[3].
In vivo, Feeding a low-choline diet containing 0.5% DL-ethionine resulted in the development of acute hemorrhagic pancreatitis with peritoneal fat necrosis in female mice within five days[4]. DL-Ethionine treatment via intraperitoneal injections for 10 days of DL-Ethionine (0.7mg/g) caused degenerative changes in rat pancreatic acinar tissue, including a widening of the endoplasmic reticulum, a reduction in the number of membrane-bound ribosomes, and the appearance of fine and bulky vacuoles containing nongranular, disordered membranes[5]. C3H female mice given 150mg/kg DL-Ethionine by intubation three times a week for 30 weeks resulted in a significant increase in the incidence of liver tumors[6].
References:
[1] Wang J, Yao H, Lu T, et al. Spectroscopic, kinetic, and theoretical analyses of oxidation of dl-ethionine by Pt (IV) anticancer model compounds[J]. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2019, 223: 117328.
[2] DeRubertis F R, Craven P A. Sequential alterations in the hepatic content and metabolism of cyclic AMP and cyclic GMP induced by DL-ethionine: Evidence for malignant transformation of liver with a sustained increase in cyclic AMP[J]. Metabolism, 1976, 25(12): 1611-1625.
[3] Kamamoto Y, Makiura S, Sugihara S, et al. The inhibitory effect of copper on DL-ethionine carcinogenesis in rats[J]. Cancer research, 1973, 33(5): 1129-1135.
[4] Lombardi B, Estes L W, Longnecker D S. Acute hemorrhagic pancreatitis (massive necrosis) with fat necrosis induced in mice by DL-ethionine fed with a choline-deficient diet[J]. The American journal of pathology, 1975, 79(3): 465.
[5] Herman L, Fitzgerald P J. The degenerative changes in pancreatic acinar cells caused by DL-ethionine[J]. The Journal of Cell Biology, 1962, 12(2): 277-296.
[6] Hoover K L, Hyde C L, Wenk M L, et al. Ethionine carcinogenesis in CD-1, BALB/c and C3H mice[J]. Carcinogenesis, 1986, 7(7): 1143-1148.