Hepatic DNA methylation and liver tumor formation in male C3H mice fed methionine- and choline-deficient diets.
The effects of the chronic administration of methyl-deficient, amino acid-defined diets on liver tumor formation were examined in male weanling C3H/HeN mice previously treated with a single ip injection of 0 or 150 mg diethylnitrosamine/kg body weight [(DENA) CAS: 55-18-5]. Five diets were used: diet 1, adequate; diet 2, devoid of both methionine and choline; diet 3, devoid of methionine only; diet 4, devoid of choline only; and diet 5, devoid of methionine, choline, folic acid, and vitamin B12. Equimolar homocystine replaced methionine in all methionine-devoid diets. All diets were administered for 1 year. No hepatocellular carcinomas and only 3 liver adenomas were seen among the 129 animals at risk in the 5 groups that had received no DENA. Among the DENA-treated groups fed diets 1-4, the incidence of hepatocellular carcinomas in the mice at risk averaged 40%, with no significant differences noted among groups. A relatively low incidence of liver carcinomas (10%) was seen among DENA-treated mice subsequently fed diet 5; it could be ascribed to the enhanced mortality seen in these animals due to the dietary deficiencies. Lung tumors were seen in 44% of the DENA-treated mice surviving more than 35 experimental weeks and in only 2.5% of the corresponding DENA-untreated animals. Feeding diet 2, deficient in methionine and choline, to male C3H mice for 5-20 weeks decreased the hepatic ratio of S-adenosylmethionine (CAS: 29908-3-0) to S-adenosylhomocysteine (979-92-0) relative to that observed in mice fed the adequate diet 1. The 5-methyldeoxycytidine [(5-MC) CAS: 838-07-3] contents of liver DNA in animals fed diet 2 for 5, 10, and 20 weeks, however, were not significantly different from the corresponding levels in diet 1-fed mice. The results indicate that a methionine- and choline-deficient dietary regimen that lowers the 5-MC levels in DNA and enhances liver tumor formation in male F344 rats does not do so in male C3H mice.
Shivapurkar
N
N
Wilson
M J
MJ
Hoover
K L
KL
Mikol
Y B
YB
Creasia
D
D
Poirier
L A
LA
D000818:Animals; D001835:Body Weight; D002794:Choline / Q000008:administration & dosage* / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000378:metabolism; D004032:Diet; D004052:Diethylnitrosamine; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000209:etiology*; D008297:Male; D008715:Methionine / Q000008:administration & dosage* / Q000378:metabolism; D008745:Methylation; D051379:Mice; D008809:Mice, Inbred C3H; D009929:Organ Size; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism; D013997:Time Factors
D003841:Deoxycytidine; D004052:Diethylnitrosamine; D012436:S-Adenosylmethionine; D004247:DNA; D012435:S-Adenosylhomocysteine; D008715:Methionine; C016569:5-methyldeoxycytidine; D002794:Choline