Fenech M, Aitken C, Rinaldi J
CSIRO Division of Human Nutrition, Adelaide SA Australia.
Carcinogenesis. 1998 Jul;19(7):1163-71. doi: 10.1093/carcin/19.7.1163.
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.
我们开展了一项横断面研究（49名男性，57名女性）以及一项随机双盲安慰剂对照饮食干预研究（每组31/32人），以确定叶酸和维生素B12（B12）对18至32岁澳大利亚年轻成年人DNA损伤（微核形成和DNA甲基化）及血浆同型半胱氨酸（HC）的影响。志愿者中无人叶酸缺乏（即红细胞叶酸<136 nmol/l），仅4.4%（均为女性）维生素B12缺乏（即血清维生素B12<150 pmol/l）。横断面研究表明，（i）男性微核细胞（MNCs）频率与血浆HC呈正相关（R = 0.293，P<0.05），（ii）女性MNC频率与血清维生素B12呈负相关（R = -0.359，P<0.01），但（iii）微核指数与叶酸状态无显著相关性。结果还表明，未甲基化CpG（DNA）水平与维生素B12或叶酸状态无显著关联。饮食干预包括在麦麸谷物中补充3.5倍推荐膳食摄入量（RDI）的叶酸和维生素B12，持续三个月，之后通过片剂补充10倍RDI的这些维生素，再持续三个月。在补充组中，初始MNC频率处于第50百分位数高位的受试者在干预期间MNC频率显著降低了25.4%，但初始MNC频率处于第50百分位数低位的受试者则无变化。MNC频率的降低与血清维生素B12（R = -0.49，P<0.0005）和血浆HC（R = 0.39，P<0.006）显著相关，但与红细胞叶酸无显著关联。补充组的DNA甲基化状态未改变。补充组中初始血浆HC处于第50百分位数高位的受试者在干预期间血浆HC下降幅度最大（达37%），且与红细胞叶酸增加显著相关（R = -0.64，P<0.0001），但与血清维生素B12无关。本研究结果表明，（i）当血浆HC低于7.5 micromol/l且血清维生素B12高于300 pmol/l时，MNC频率降至最低，（ii）每日补充700微克叶酸和7微克维生素B12足以使MNC频率和血浆HC降至最低。因此，血浆HC升高这一心血管疾病风险因素似乎也可能是染色体损伤的风险因素。
