Reversibility of changes in nucleic acid methylation and gene expression induced in rat liver by severe dietary methyl deficiency.

As we have reported previously, both DNA and tRNA become hypomethylated in livers of rats fed a cancer promoting, methyl-deficient diet (MDD) for as short a period as one week. Within the same period, activities of tRNA and DNA methyltransferases (MTases) increase and levels of mRNAs for several genes believed to have roles in growth regulation are altered. These diet-induced changes in nucleic acid methylation and gene expression increased in extent when MDD was fed continuously for four weeks.

Alterations in expression and methylation of specific genes in livers of rats fed a cancer promoting methyl-deficient diet.

We have reported earlier that hypomethylated DNA is rapidly induced in the livers of male Fischer rats fed an extremely methyl-deficient diet (MDD). The early effects of dietary methyl deficiency on the expression of several genes in the livers of such animals have now been investigated. Poly(A)+ RNA was isolated from the livers of rats fed MDD or a similar diet supplemented with adequate supplies of choline, methionine, folic acid and vitamin B12 (CSD) for periods ranging from 1 to 4 weeks.

Isolation of cDNA clones for the interferon-induced 67,000-dalton protein: direct induction of a family of mRNAs by human interferon-alpha and interferon-gamma.

A partial cDNA clone for the interferon (IFN)-induced 67,000-dalton (67K) protein was isolated by immunological screening and used as a probe to study the expression of mRNAs encoding this protein. Northern blot analyses of RNA from IFN-treated GM2767 cells revealed the presence of two major 67K-specific RNA species, 2.7 and 4.

Prolonged survival of female AKR mice fed diets supplemented with methionine and choline.

Female mice of the AKR/J (AK) strain were fed a control diet (Purina Rodent Laboratory Chow) or a lipotrope-supplemented diet (Purina Rodent Chow plus 2% D,L-methionine and 1% choline chloride) beginning at 1 day after weaning. Food consumption and weight gain were found to be the same in both groups of animals. Mice of this inbred strain spontaneously develop thymic lymphoma, with close to 100% mortality expected by 12-13 months of age.

Rapid appearance of hypomethylated DNA in livers of rats fed cancer-promoting, methyl-deficient diets.

Prolonged intake of diets deficient in sources of methyl groups leads to development of hepatomas in rats and promotes chemical carcinogenesis in both rats and certain strains of mice. Since methylation of cytosine residues in regulatory regions can affect gene activity, several investigators have postulated that the effects of methyl-deficient diets on tumorigenesis result from the inability of cells to maintain normal patterns of DNA methylation. However, significant decreases in the 5-methylcytosine content of liver DNA have not been reported to occur until rats have consumed methyl-deficient diets for several months.