Reduction of the genomic damage level in haemodialysis patients by folic acid and vitamin B12 supplementation.
BACKGROUND
Cancer incidence and genomic damage of peripheral lymphocytes are elevated in patients with end-stage renal failure. Among other uraemic toxins, homocysteine (Hcy) levels are increased in most of these patients. In healthy individuals, plasma Hcy correlates with the degree of genomic damage observed in peripheral blood lymphocytes (PBL). The accumulation of Hcy can be reduced by supplementation with folic acid and vitamin B12. The aim of this study was to analyse whether this supplementation can also lower the genomic damage in PBL of haemodialysis patients. This may ultimately help to reduce cancer incidence in renal patients.


METHODS
In a prospective study with 27 patients, we analysed the genomic damage in dialysis patients before and at different time points after the initiation of folate/vitamin B12 supplementation. Genomic damage was measured by the frequency of micronuclei, a subset of chromosomal aberrations, in PBL.


RESULTS
Supplementation with folic acid and vitamin B12 (more markedly with both) reduced the micronucleus frequency in PBL of dialysis patients. This was not mediated by altered lymphocyte proliferation capacity or changes in DNA cytosine-methylation. Plasma-Hcy was lowered more efficiently by the combined folic acid/vitamin B12 supplementation, and lymphocyte DNA of this group exhibited a nonsignificant trend for a reduction of 1,N(6)-etheno-2'-deoxyadenosine, a marker for oxidative stress.


CONCLUSIONS
A reduction of the genomic damage in PBL can be achieved in dialysis patients by supplementation with folic acid and vitamin B12. This may be mediated by Hcy reduction.
Stopper
Helga
H
Department of Toxicology, University of Wuerzburg, Versbacher Strasse 9, D-97078 Wuerzburg, Germany. stopper@toxi.uni-wuerzburg.de
Treutlein
Anna-Teresa
AT
Bahner
Udo
U
Schupp
Nicole
N
Schmid
Ursula
U
Brink
Andreas
A
Perna
Alessandra
A
Heidland
August
A
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004249:DNA Damage / Q000235:genetics*; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D015894:Genome, Human / Q000187:drug effects; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000235:genetics / Q000628:therapy; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D015162:Micronucleus Tests; D008875:Middle Aged; D009369:Neoplasms / Q000209:etiology / Q000235:genetics / Q000517:prevention & control; D011446:Prospective Studies; D006435:Renal Dialysis / Q000009:adverse effects*; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000494:pharmacology*
D006710:Homocysteine; D005492:Folic Acid; D014805:Vitamin B 12