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European Journal of Nutrition

, Volume 48, Issue 7, pp 429–436 | Cite as

Mitochondrial DNA deletions of blood lymphocytes as genetic markers of low folate-related mitochondrial genotoxicity in peripheral tissues

  • Yi-Fang Chou
  • Rwei-Fen S. HuangEmail author
Original Contribution

Abstract

Background

A low folate status and mitochondrial DNA (mtDNA) mutations are risk factors for various cancers and degenerative diseases. It is not known if lymphocytic mtDNA deletions can be used as genetic “markers” to reflect global mtDNA damage during folate deficiency.

Aim of the study

The aim of this study was to characterize folate-related mtDNA deletions in lymphocytes and their associations with mt genotoxicity in peripheral tissues.

Methods

Weaning Wistar rats were fed folate-deficient and folate-replete (control) diets for 2 and 4 weeks. Folate levels of blood lymphocytes and various tissues were assayed by the Lactobacillus casei method. mtDNA deletions were measured by a real-time polymerase chain reaction analysis of whole DNA extracts.

Results

Compared to the control counterparts, mtDNA deletions of lymphocytes increased by 3.5-fold (P < 0.05) after 4 weeks of folate deficiency. Lymphocytic mtDNA deletions were inversely associated with plasma (r = −0.619, P = 0.018), red blood cell (r = −0.668, P = 0.009), and lymphocytic folate levels (r = −0.536, P = 0.048). Frequencies of lymphatic mtDNA deletions were positively correlated with mtDNA deletions in tissues including the lungs (r = 0.803, P = 0.0005), muscles (r = 0.755, P = 0.001), heart (r = 0.633, P = 0.015), liver (r = 0.722, P = 0.003), kidneys (r = 0.737, P = 0.006), pancreas (r = 0.666, P = 0.009), and brain (r = 0.917, P < 0.0001). Conclusions: Our data demonstrate that accumulated mtDNA deletions of lymphocytes depended upon dietary folate deprivation. The accumulated mt deletions in lymphocytes closely reflected the mt genotoxicity in the peripheral tissues during folate deficiency.

Keywords

Folate deficiency mtDNA deletions Lymphocytes Genetic marker Peripheral tissues 

Abbreviations

FD

Folate-deficient

mt

Mitochondrial

mtDNA4834 deletion

4,834-bp large deletion in mtDNA

ROS

Reactive oxygen species

RE

Relative expression

Notes

Acknowledgments

The authors are deeply grateful to Prof. Y.-H. Wei of the Department of Biochemistry at National Yang-Ming University, Taipei, Taiwan for his kind support and invaluable advice on mtDNA mutations. This study was supported by a grant (NSC96-2320-B-002) from the National Science Council, Taiwan to R.F.S. Huang.

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Department of Nutritional ScienceFu-Jen UniversityHsinchuangTaiwan

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