Folate deficiency causes DNA breaks like ionizing radiation

[youngsinatra]

"DNA double-strand breaks, the most serious DNA lesion caused by ionizing radiation, are also caused by several vitamin or mineral deficiencies, such as for folate. Primary human lymphocytes were either irradiated or cultured at different levels of folate deficiency to assess cell proliferation, apoptosis, cell cycle, DNA breaks, and changes in gene expression. Both radiation and folate deficiency decreased cell proliferation and induced DNA breaks, apoptosis, and cell cycle arrest. Levels of folate deficiency commonly found resulted in effects similar to those caused by 1 Gy of radiation, a relatively high dose. Though both radiation and folate deficiency caused DNA breaks, they affected the expression of different genes. Radiation activated excision and DNA double-strand break repair genes and repressed mitochondrially encoded genes. Folate deficiency activated base and nucleotide excision repair genes and repressed folate-related genes. No DNA double-strand break repair gene was activated by folate deficiency. These findings suggest that a diet poor in folate may pose a risk of DNA damage comparable to that of a relatively high dose of radiation. Our results also suggest that research on biological effects of low-dose radiation should take into account the nutritional status of the subjects, because folate deficiency could confound the effects of low-dose radiation."
- https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.03-0382fje

 

[Peachy]

Interesting. That explains the increased risk of cancer in people with the MTHFR C677T polymorphism.

I still haven’t worked out whether methylfolate is a yay or nay. If it corrects the folate deficiency, seems it would help prevent DNA damage and resolve the “aberrant” methylation, not encourage it.

“Folate functions as methyl donor in the one carbon metabolism pathway, an essential process in DNA synthesis, repair and methy- lation and dysregulation of the folate metabolic pathway either due to deficiency of folate or MTHFR C677T polymorphism could result in carcinogenesis [10,61].

There are two important mecha- nisms by which folate deficiency may influence the risk of cancer: (i) by inducing misincorporation of uracil into DNA, which can lead to chromosomal breaks and mutations [60,62,63], and/or (ii) by causing aberrant DNA methylation, resulting in altered expression of critical proto-oncogenes and tumor suppressor genes.”

https://www.ajol.info/index.php/ejhg/article/download/181774/171160