Carcinogenesis, Vol 18, 1329-1336, Copyright © 1997 by Oxford University Press
MF Fenech, IE Dreosti and JR Rinaldi
Deficient levels of folic acid and vitamin B12 are associated with elevated
chromosome damage rate and high concentrations of homocysteine in the
blood. We have therefore performed a study to determine the prevalence of
folate deficiency, vitamin B12 deficiency and hyperhomocysteinemia in 64
healthy men aged between 50 and 70 years, and evaluate the relationship of
these micronutrient levels in the blood with the micronucleus frequency in
peripheral blood lymphocytes. We also performed a placebo-controlled,
double-blind intervention study to determine whether supplementation of the
diet with a daily dose of 0.7 mg (as a supplement in cereal) or 2.0 mg (in
a tablet) over a period of 4 months resulted in a significant alteration of
folate status, homocysteine status and the micronucleus index. Twenty-three
per cent of the men were serum folate deficient (<6.8 nmol/l), 16% were
red blood cell folate deficient (<317 nmol/l), 4.7% were vitamin B12
deficient (<150 pmol/l) and 37% has plasma homocysteine levels >10
micromol/l. In total, 56% of the men had one or more abnormal blood values
for folate, vitamin B12 or homocysteine. The micronucleus index of these
men (n = 34) in cytokinesis-blocked binucleated cells (19.2 +/- 1.1) was
significantly elevated (P = 0.02) when compared to the micronucleus index
of the rest of the men who had normal levels of folate, vitamin B12 and
homocysteine (16.3 +/- 1.3, n = 30). Interestingly, the micronucleus index
in men with normal folate and vitamin B12, but homocysteine levels >10
micromol/l (19.4 +/- 1.7, n = 15) was also significantly higher (P = 0.05)
when compared to those with normal folate, vitamin B12 and homocysteine.
This novel result was also supported by the observation that the
micronucleus index and plasma homocysteine were significantly (P = 0.0086)
and positively correlated (r2 = 0.172) in those subjects who were not
deficient in folate or vitamin B12. The micronucleus index was not
significantly correlated with folate indices, but there was a significant
(P = 0.013) negative correlation with serum vitamin B12 (r2 = 0.099). Daily
supplementation of the diet with 0.7 mg free folic acid in cereal for 2
months followed by 2.0 mg free folic acid via a tablet produced a 4- fold
increase in plasma folate, a 2.6-fold increase in red blood cell folate and
a 11% reduction in plasma homocysteine; however, these changes were not
accompanied by a reduction in the micronucleus index. In conclusion, it is
apparent that elevated homocysteine status, in the absence of vitamin
deficiency and low, but not deficient, vitamin B12 status are important
risk factors for increased chromosome damage in lymphocytes.
ARTICLES
Folate, vitamin B12, homocysteine status and chromosome damage rate in lymphocytes of older men
CSIRO Division of Human Nutrition, Adelaide, Australia.
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