Carcinogenesis, Vol 19, 1163-1171, Copyright © 1998 by Oxford University Press
M Fenech, C Aitken and J Rinaldi
We performed a cross-sectional study (n = 49 males, 57 females) and a
randomized double-blind placebo-controlled dietary intervention study (n =
31/32 per group) to determine the effect of folate and vitamin B12 (B12) on
DNA damage (micronucleus formation and DNA methylation) and plasma
homocysteine (HC) in young Australian adults aged 18-32 years. None of the
volunteers were folate deficient (i.e. red blood cell folate <136
nmol/l) and only 4.4% (all females) were vitamin B12 deficient (i.e. serum
vitamin B12 <150 pmol/l). The cross-sectional study showed that (i) the
frequency of micronucleated cells (MNCs) was positively correlated with
plasma HC in males (R = 0.293, P < 0.05) and (ii) in females MNC
frequency was negatively correlated with serum vitamin B12 (R = -0.359, P
< 0.01) but (iii) there was no significant correlation between
micronucleus index and folate status. The results also showed that the
level of unmethylated CpG (DNA) was not significantly related to vitamin
B12 or folate status. The dietary intervention involved supplementation
with 3.5x the recommended dietary intake (RDI) of folate and vitamin B12 in
wheat bran cereal for three months followed by ten times the RDI of these
vitamins via tablets for a further three months. In the supplemented group,
MNC frequency was significantly reduced during the intervention by 25.4% in
those subjects with initial MNC frequency in the high 50th percentile but
there was no change in those subjects in the low 50th percentile for
initial MNC frequency. The reduction in MNC frequency was significantly
correlated with serum vitamin B12 (R = -0.49, P < 0.0005) and plasma HC
(R = 0.39, P < 0.006), but was not significantly related to red blood
cell folate. DNA methylation status was not altered in the supplemented
group. The greatest decrease in plasma HC (by 37%) during the intervention
was observed in those subjects in the supplemented group with initial
plasma HC in the high 50th percentile, and correlated significantly with
increases in red blood cell folate (R = -0.64, P < 0.0001) but not with
serum vitamin B12. The results from this study suggest that (i) MNC
frequency is minimized when plasma HC is below 7.5 micromol/l and serum
vitamin B12 is above 300 pmol/l and (ii) dietary supplement intake of 700
microg folic acid and 7 microg vitamin B12 is sufficient to minimize MNC
frequency and plasma HC. Thus, it appears that elevated plasma HC, a risk
factor for cardiovascular disease, may also be a risk factor for chromosome
damage.
ARTICLES
Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults
CSIRO Division of Human Nutrition, Adelaide SA Australia.
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