Ethionine carcinogenesis in CD-1, BALB/c and C3H mice

In two separate in vivo studies, ethionine was evaluated forcarcinogenic activity in mice. In the first study, DL-ethioninewas fed in a chow diet at 0 (controls), 0.1 (low dose, LD) and0.25% (high dose, HD) concentrations to the following groupsof mice (30 animals/group): Swiss Webster CD-I females, BALB/cmales, and C3H/HeN males and females. Because of severe toxicity,BALB/c females were fed 0.05% (LD) and 0.1% (HD) ethionine.The Swiss and BALB/c mice were maintained on their respectivediets for up to 105 weeks before killing whereas the C3H micewere killed at 68 weeks because of the high spontaneous incidenceof liver tumors hi this strain. Hie percentages of animals atrisk (surviving the time to the first liver tumor recorded ineach sex and strain) that bore liver tumors were as follows:Swiss female control, 0% (0/29), Swiss female LD, 87% (20/23);Swiss female HD, 89% (16/18); C3H male controls, 35% (8/23);C3H male LD, 55% (16/29); C3H male HD, 58% (15/26); C3H femalecontrols, 5% (1/20); C3H female LD, 60% (12/20); C3H femaleHD, 92% (12/13); BALB/c male controls, 4% (1/23); BALB/c maleLD, 8% (2/24); BALB/c male HD, 31% (5/16); BALB/c female controls,0% (0/30); BALB/c female LD, 52% (14/27); and BALB/c femaleHD, 92% (12/13). The female mice were more responsive than themales hi developing liver tumors. The results of the feedingstudy are compared with those obtained in a second study hiwhich C3H female mice were in-tubated with 0, 150 or 500 mgDL-ethionine/kg body wt three times per week for 30 weeks andkilled at 2 years. Only the LD mice showed a significantly increasedincidence of liver tumors (20/39) as compared to controls (12/41)or HD mice (7/37) hi the latter study. The hepatic levels ofthe major ethionine metabolite and methylase inhibitor, S-adenosyl-ethionine(AdoEt), as well as of the endogenous methyl group donor, S-adenosylmethionine(AdoMet) were determined in Swiss female mice fed either 0.1or 0.3% in the diet for 1–6 weeks. Hepatic AdoEt levelsranged from 37 to 80 /ig/g h'ver hi the LD animals and from61 to 203 /ig/g liver in the HD group; levels of the endogenousmetabolite AdoMet correspondingly dropped to 65% of the normallevels. The present results (0 extend to different strains andto both sexes previous observations demonstrating the hepatocarcinogenkactivity of ethionine hi mice; and (ii) indicate that as hithe rat such activity may be exerted through the formation ofAdoEt.