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脐带血中的全球DNA甲基化作为产前铅和锑暴露的生物标志物

Global DNA Methylation in Cord Blood as a Biomarker for Prenatal Lead and Antimony Exposures.

作者信息

Okamoto Yoshinori, Iwai-Shimada Miyuki, Nakai Kunihiko, Tatsuta Nozomi, Mori Yoko, Aoki Akira, Kojima Nakao, Takada Tatsuyuki, Satoh Hiroshi, Jinno Hideto

机构信息

Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan.

Health and Environmental Risk Research Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba 305-8506, Japan.

出版信息

Toxics. 2022 Mar 26;10(4):157. doi: 10.3390/toxics10040157.

Abstract

DNA methylation is an epigenetic mechanism for gene expression modulation and can be used as a predictor of future disease risks. A prospective birth cohort study was performed to clarify the effects of neurotoxicants on child development, namely, the Tohoku Study of Child Development, in Japan. This study aimed to evaluate the association of prenatal exposure to five toxic metals-arsenic, cadmium, mercury, lead (Pb), antimony (Sb), and polychlorinated biphenyls (PCBs, N = 166)-with global DNA methylation in umbilical cord blood DNA. DNA methylation markers, 5-methyl-2'-deoxycytidine (mC) and 5-hydroxymethyl-2'-deoxycytidine (hmC), were determined using liquid chromatography-tandem mass spectrometry. The mC content in cord blood DNA was positively correlated with Pb and Sb levels ( = 0.435 and 0.288, respectively) but not with cord blood PCBs. We also observed significant positive correlations among Pb levels, maternal age, and hmC content ( = 0.155 and 0.243, respectively). The multiple regression analysis among the potential predictors demonstrated consistent positive associations between Pb and Sb levels and mC and hmC content. Our results suggest that global DNA methylation is a promising biomarker for prenatal exposure to Pb and Sb.

摘要

DNA甲基化是一种用于调节基因表达的表观遗传机制,可作为未来疾病风险的预测指标。在日本进行了一项前瞻性出生队列研究,以阐明神经毒物对儿童发育的影响,即东北儿童发育研究。本研究旨在评估产前暴露于五种有毒金属——砷、镉、汞、铅(Pb)、锑(Sb)和多氯联苯(PCBs,N = 166)与脐带血DNA中整体DNA甲基化之间的关联。使用液相色谱-串联质谱法测定DNA甲基化标记物5-甲基-2'-脱氧胞苷(mC)和5-羟甲基-2'-脱氧胞苷(hmC)。脐带血DNA中的mC含量与Pb和Sb水平呈正相关(分别为 = 0.435和0.288),但与脐带血PCBs无关。我们还观察到Pb水平、母亲年龄和hmC含量之间存在显著正相关(分别为 = 0.155和0.243)。潜在预测因素之间的多元回归分析表明,Pb和Sb水平与mC和hmC含量之间存在一致的正相关。我们的结果表明,整体DNA甲基化是产前暴露于Pb和Sb的一个有前景的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ced/9027623/1d4baf9ebb40/toxics-10-00157-g001.jpg

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