Disease relevance of Ethionine

• Young female mice fed a choline-deficient, ethionine-supplemented (CDE) diet rapidly develop acute hemorrhagic pancreatitis [1].
• The findings suggest that a CD diet alters the response of rat liver to DL-ethionine and leads to an early and enhanced induction of hepatocellular carcinoma [2].
• PGE2 did not protect against the weight loss, decrease in food consumption, alteration in serum amylase, pancreatic necrosis, or mortality induced by ethionine [3].
• The present study shows that 10 mM ethionine prevents the thermal induction of lambda-prophage in a tif-1 derivative of E. coli [4].
• In regenerating rat liver, histone synthesis was inhibited by only 20 to 30% with large doses of ethionine (0.75 to 1.0 mg/g body weight) [5].

High impact information on Ethionine

• Large increases in frequency of HAT+ cells were obtained by treatment with n-butyrate and L-ethionine, which affect gene expression in other cell systems but have no known mutagenic potential [6].
• Induction of ovalbumin and conalbumin synthesis in immature chick oviducts by ethionine [7].
• Then, acute pancreatitis was induced either by caerulein injections, or by feeding a choline-deficient, ethionine-supplemented (CDE) diet [8].
• Edematous pancreatitis was induced in rats by hyperstimulation with cerulein and hemorrhagic pancreatitis was induced in mice by feeding a choline-deficient, ethionine-supplemented diet [9].
• Cytoskeletal and adhesion characteristics of DL-ethionine (CAS: 67-21-0)-transformed rat liver epithelial cells (ETC) were compared with those of nontumorigenic, untreated cells of the same cell line both at the same passage level as ETC and at an early low passage level [10].

Chemical compound and disease context of Ethionine

• A new common antigen, preneoplastic (PN), was found in every early and late hyperplastic nodule and in every primary hepatoma induced by N-2-fluorenylacetamide, ethionine, 3-methyl-4-dimethylaminoazobenzene, dimethylnitrosamine, or diethylnitrosamine in three strains of rats (CFN, F344, and BUF) [11].
• The effect of prostaglandin E2 on ethionine-induced pancreatitis in the rat [3].
• The tRNA methyltransferases from normal rat liver and Novikoff hepatoma have been compared with respect to their base specificity, capacity to methylate, and reaction kinetics, using mixed Escherichia coli B transfer RNA (tRNA) and ethionine-induced partially methyl-deficient rat liver tRNA [12].
• Methyl-deficient transfer RNA (tRNA) and subnormal levels of tRNA-methylating enzymes were found in the livers of female rats that had received injections of 250 mg DL-ethionine per kg body weight per day and 120 mg adenine per kg body weight per day for 2 days [13].
• Conversion of 5-S-ethyl-5-thio-D-ribose to ethionine in Klebsiella pneumoniae. Basis for the selective toxicity of 5-S-ethyl-5-thio-D-ribose [14].

Biological context of Ethionine

• The extent of zygotic cpDNA methylation was shown to be dependent on the preexisting methylation level of both parental gametic cpDNAs . L-Ethionine and 5-azacytidine effectively inhibited cpDNA methylation during gametogenesis and ensuing zygotic development as shown by both Hpa II/Msp I digestion patterns and HPLC [15].
• We examined the expression of six proto-oncogenes in (i) whole rat liver and isolated liver cell populations during the course of hepatocarcinogenesis induced by a choline-deficient diet containing 0.1% ethionine and (ii) fetal rat liver at different stages of development [16].
• Finally, rats fed the choline-free diet with 0.1% ethionine had massive oval cell proliferation and progressive loss of parenchymal liver tissue [17].
• Elevated transcriptional complexity and decrease in enzymatic DNA methylation in cells treated with L-ethionine [18].
• This paper analyzes the extent of enzymatic methylation of DNA in P815 cells cultured for several cell cycles in the presence of 1 mM L-ethionine by use of the bacterial restriction enzymes HpaII, MspI, HhaI, HaeII, and AvaI [18].

Anatomical context of Ethionine

• To evaluate this concept, the effect of feeding a choline-deficient diet supplemented with 0.5% DL-ethionine was determined in 4 and 6-wk-old mice in which the reticuloendothelial system was normal, stimulated, or depressed [19].
• Pancreas acinar cell regeneration and histone (H1 and H10) modifications after partial pancreatectomy or after a protein-free ethionine regimen [20].
• Functional and structural alterations of liver ergastoplasmic membranes during DL-ethionine hepatocarcinogenesis [21].
• Oval cells and biliary epithelial cells were isolated from livers of rats fed a choline-deficient diet containing 0.1% ethionine and from normal rat livers, respectively [22].
• Different functional and structural properties of rat liver microsomes were studied during hepatocarcinogenesis induced by 0.25% DL-ethionine [21].

Associations of Ethionine with other chemical compounds

• This effect of AdoMet was mimicked by methionine, and blocked by 3-deazaadenosine and L-ethionine, but not D-ethionine, indicating that the effect was specific and mediated probably by a methylation reaction [23].
• This methyl-deficient tRNA from liver can be methylated in vitro by enzymes from normal or ethionine-treated rats [24].
• These studies provide a mechanism by which ethionine through S-adenosylethionine may alter the methylation of DNA in Friend erythroleukemic cells [25].
• When the ethionine plus adenine injections were continued for longer periods of time, liver tRNA-methylating enzyme activity measured in vitro gradually increased and exceeded that of the controls [13].
• Dietary 2-acetylaminofluorene, 3'-methyl-4-dimethylaminoazobenzene, aflatoxin B1, ethionine, and diethylnitrosamine rapidly induced resistance to doses of Adriamycin, methotrexate, cycloheximide, and aflatoxin B1 which were cytocidal to normal hepatocytes from untreated rats [26].

Gene context of Ethionine

• Absence of p53 allows a cell to cycle past the normal Hayflick limit, rendering it immortalized, although subsequent genetic alterations are thought necessary for transformation. p53 knockout mice were fed a choline-deficient, ethionine-supplemented diet, previously shown to increase oval cell numbers in wild-type mice [27].
• We observed increased liver expression of PPARalpha and gamma in concert with expanding oval cell numbers during the first 21 days following commencement of the choline deficient, ethionine supplemented (CDE) dietary model of carcinogenic liver injury in mice [28].
• This conversion was essential for growth inhibition by ethionine because metE mutants which were deficient in S-adenosylmethionine synthetase activity, were resistant to 10 mM ethionine and converted only a small amount of ethionine to SAE [29].
• The comparative effects of the subchronic administration to rats of ethionine-supplemented and of chemically defined methyl-deficient diets on the hepatic levels of S-adenosylmethionine (SAM) and of ornithine decarboxylase (ODC), an enzyme marker of cell proliferation, were studied [30].
• In rats maintained on a carcinogenic diet (choline deficient containing 0.1% ethionine), the levels of c-myc and p53 mRNAs increased by 4 wk after animals were placed on the diet [31].

Analytical, diagnostic and therapeutic context of Ethionine

• Acute pancreatitis was induced by daily intraperitoneal injections of DL-ethionine in rats maintained on a protein-free diet [3].
• Ethionine, a liver carcinogen, was administered p.o. (300 mg/kg) to rats 17 hr after partial hepatectomy [32].
• Destruction of acinar tissue by duct ligation or ethionine treatment is followed by rapid regeneration [33].
• Indirect immunofluorescence analysis of PHC induced by ethionine in a choline-deficient diet or by the Solt/Farber protocol showed that 52% and 65% of the persistent hepatic nodules induced by ethionine in a choline-deficient diet and by the Solt/Farber protocol, respectively, were unreactive with MAb 362.50 [34].
• The tRNA extracted from the livers of rats was active as a substrate for in vitro methylation with extracts from normal rat liver 19 h after treatment with L-ethionine (35 mg/100 g/24 h) [35].

References