Vitamin B 12 and methionine metabolism in the Buffalo rat liver and Morris 5123 hepatoma
Iseri, O.A.; Gottlieb, L.S.; Hegsted, D.M.; Vitale, J.J.
Laboratory Investigation; a Journal of Technical Methods and Pathology 27(2): 226-235
1972
ISSN/ISBN: 0023-6837 PMID: 4341274 Document Number: 47056
Weanling Buffalo rats of mean weight 39 g in 6 groups of 12 rats were given a basal diet (NAR 40, 7280) low in methionine and lacking choline and vitamin B-12 but with enough folacin; the homocystine content if all were methylated would give rise to enough methionine to promote substantial growth. Five groups had with the basal diet vitamin B-12, 4, 16, 64, 260 or 1000 mu g/kg diet. After 1 week on the diets half the rats of each group were given a subcutaneous implant of Morris 5123 hepatoma and 7 weeks later all were killed. A second experiment was similar except that the rats were depleted of vitamin B-12 for 8 weeks after tumour implant before division into treatment groups and given choline, methionine or vitamin B-12 for 3 weeks. A third study compared Buffalo with Charles River rats when from 28 days of age they were given for 8 weeks the deficient diet alone or with vitamin B-12 8 or 200 mu g/kg, methionine 3 g/kg or choline 3 g/kg diet.Buffalo rats with or without tumours developed grossly fatty livers with all vitamin B-12 intakes. Tumours were of widely different sizes but with low vitamin B-12 intake they tended to be small and mainly cystic with small solid areas and with high vitamin B-12 intake larger tumours had large solid areas as well as some cysts and the largest tended to have focal necrosis and haemorrhage; there was almost no visible fat in hepatoma cells. In the second experiment vitamin B-12 stimulated weight gain, so did choline or methionine. The vitamin did not mobilize any appreciable amount of fat from the liver or prevent the development of early cirrhosis in 3 of 5 rats with and 1 of 4 without hepatoma; choline or methionine removed much of the liver fat in 3 weeks and prevented cirrhosis. In the third trial growth response to vitamin B-12 was consistently higher in CR than in Buffalo rats, so was haematological response, and livers of CR rats showed less fat with increasing amounts of vitamin B-12 or methionine and none with choline, though Buffalo rat livers remained fatty with all vitamin B-12 supplements or methionine but were not fatty with choline. It is concluded that the Buffalo rat has a genetic defect in the enzyme system involved in the synthesis of methyl groups and the transfer of one-carbon units.