叶酸对1,3-丁二烯诱发的小鼠DNA低甲基化和染色体损伤的影响

doi:10.3969/j.issn.1004-616x.2017.03.006

Abstract

Abstract: OBJECTIVE:To explore the effect of folic acid (FA) on genetic damage and DNA methylation which were induced by 1,3-butadiene (BD) in mice. METHODS:Male Kunming mice were fed with corresponding diets for 3 weeks to establish FA-C (normal folic acid group),FA-D (folic acid deficiency group) and FA-S (folic acid supplementation group) animal models. Then,each group of FA-treated mice was randomly divided into control,and BD low-and high-dose groups (0,13.82,1 382.14 mg/m³) and treated with the corresponding dosages of BD by inhalation for 2 weeks (6 h/d,5 d/week). Enzyme-linked immunosorbent assay (ELISA) was applied to detect the concentrations of FA in serum and genomic DNA methylation levels in liver tissue. The expression of methyltransferase DNMT1 and DNMT3a was quantified by qPCR and chromosomal damage in peripheral blood lymphocytes was detected by cytokinesis-block micronucleus test (CBMNT). RESULTS:After 3 weeks of FA treatment,the concentrations of serum folic acid were significantly lower in FA-D group but higher in FA-S group compared with the FA-C group. With increase of the BD doses,methylation of global DNA and expression of methyltransferase were decreased while the frequencies of micronuclei,nucleoplasmic bridge and nuclear bud were increased within the same FA treated group. On the other hand,under the same BD exposure conditions,FA-D group showed a decreased level of DNA methylation and methyltransferase expression and increased chromosomal damage while FA-S group resulted in an increased level of DNA methylation and mRNA level of methyltransferase 1,3a expression and decreased micronucleus rate of chromosome compared with FA-C group,especially in the high dose BD exposure conditions (P < 0.05 or 0.01). CONCLUSION:BD can induce global DNA demethylation and chromosomal damage in mice. Folic acid deficiency can aggravate the BD-induced abnormalities. However,folic acid supplementation has a protective effect against the BD-induced abnormalities.

Key words: folic acid, 1, 3-butadiene, DNA methylation, cytokinesis-block micronucleus test

CLC Number:

R394.6

WANG Zhi, LING Xi, ZHANG Guowei, GAO Jianfang, ZOU Peng, JING Che, LIN Zhetao, LIU Jinyi, CAO Jia, AO Lin. Effect of folic acid on DNA demethylation and chromosomal damage in mice after their inhalation exposure to 1, 3-butadiene[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2017, 29(3): 189-193.

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Effect of folic acid on DNA demethylation and chromosomal damage in mice after their inhalation exposure to 1, 3-butadiene

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