Inhibition of hepatocarcinogenesis in mice by dietary methyl donors methionine and choline.
A dietary deficiency of methyl donors, the lipotropes methionine and choline, enhances the activity of hepatocarcinogens in rodents. To determine if the reverse is true, an excess of dietary choline, methionine, or both was fed to male mice given a carcinogenic dose of aflatoxin B1 (AFB1). Fifty weeks following the last dose of AFB1, all survivors were killed then examined for tumor incidence, and samples of nontumorous liver tissue were assayed for activities of mixed function oxidases (MFO). Survival was best in the high-methionine/high-choline group, with 36/38 surviving to termination of the study. Survival in the other groups was 35/38, 30/70, 33/38, and 34/37 in control with no AFB1, control with AFB1, groups with high methionine, and high choline, respectively. Combined adenoma/carcinoma incidence was 8/38, 30/37, 21/38, 20/37, and 10/38 in groups control with no AFB1, control with AFB1, high methione with AFB1, high choline with AFB1, and high choline and high methionine with AFB1, respectively. Cytochrome P450, cytochrome B5, cytochrome C, and ethylmorphine N-demethylase activities were all increased over controls, with most marked increases in the cytochrome P450 and ethylmorphine N-demethylase activities. The data presented here document a protective effect of dietary methyl donors on AFB1-induced hepatocarcinogenesis in mice probably acting, in part, via activation/detoxification mechanisms favoring an increased balance in detoxification of AFB1.
Newberne
P M
PM
Department of Pathology, Mallory Institute, Boston University School of Medicine, MA 02118.
Suphiphat
V
V
Locniskar
M
M
de Camargo
J L
JL
D016604:Aflatoxin B1; D000348:Aflatoxins; D000818:Animals; D002273:Carcinogens; D002794:Choline / Q000008:administration & dosage*; D004032:Diet; D015993:Life Tables; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D008297:Male; D008715:Methionine / Q000008:administration & dosage*; D051379:Mice; D006899:Mixed Function Oxygenases / Q000378:metabolism
D000348:Aflatoxins; D002273:Carcinogens; D016604:Aflatoxin B1; D008715:Methionine; D006899:Mixed Function Oxygenases; D002794:Choline