Diet-induced DNA damage and altered nucleotide metabolism in lymphocytes from methyl-donor-deficient rats.

Abstract:

:Tumor induction with chronic feeding of methyl-donor-deficient diets has been well established; however, the biochemical and molecular mechanisms which predipose to tumorigenesis in this model are still not well understood. The purpose of the present investigation was to assess DNA damage and altered nucleotide metabolism in lymphocytes from Fischer 344 rats fed one of four semi-purified diets: (i) deficient in methionine and choline; (ii) deficient in folic acid; (iii) deficient in methionine, choline and folic acid; or (iv) a supplemented control diet. The accumulation of DNA-strand breaks, as assessed by DNA unwinding in alkali, was increased in lymphocytes from both the methionine/choline-deficient and folate-deficient groups, but was most severe in the group deficient in all three methyl donors. Lymphocyte DNA damage was consistently associated with alterations in folate-dependent thymidylate synthesis, and a decrease in intracellular levels of the DNA-repair-associated pyridine nucleotide, nicotinamide adenine dinucleotide. In the liver, a synergistic lipotropic interaction between folate deficiency and methionine/choline deficiency was observed, confirming the metabolic inter-relationship between these nutrients. Taken together, the results suggest that folate deficiency interacts with methionine/choline deficiency to potentiate symptoms of methyl-donor deficiency and that alterations in folate-dependent thymidylate synthesis are related to DNA damage in lymphocytes. These metabolic aberrations may contribute to immune dysfunction with chronic feeding of methyl-donor-deficient diets.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

James SJ,Yin L

doi

10.1093/carcin/10.7.1209

subject

Has Abstract

pub_date

1989-07-01 00:00:00

pages

1209-14

issue

7

eissn

0143-3334

issn

1460-2180

journal_volume

10

pub_type

杂志文章