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镉暴露与DNA损伤(遗传毒性):一项系统综述与荟萃分析

Cadmium exposure and DNA damage (genotoxicity): a systematic review and meta-analysis.

作者信息

Nagaraju Raju, Kalahasthi Ravibabu, Balachandar Rakesh, Bagepally Bhavani Shankara

机构信息

Department of Biochemistry, Regional Occupational Health Centre (Southern), ICMR-National Institute of Occupational Health, Bengaluru, India.

Department of Clinical Epidemiology, ICMR-National Institute of Occupational Health, Ahmedabad, India.

出版信息

Crit Rev Toxicol. 2022 Nov;52(10):786-798. doi: 10.1080/10408444.2023.2173557. Epub 2023 Feb 21.

DOI:10.1080/10408444.2023.2173557
PMID:36802997
Abstract

Existing literature suggests an association between chronic cadmium (Cd) exposure and the induction of DNA damage and genotoxicity. However, observations from individual studies are inconsistent and conflicting. Therefore current systematic review aimed to pool evidence from existing literature to synthesize quantitative and qualitative corroboration on the association between markers of genotoxicity and occupational Cd exposed population. Studies that evaluated markers of DNA damage among occupationally Cd-exposed and unexposed workers were selected after a systematic literature search. The DNA damage markers included were chromosomal aberrations (chromosomal, chromatid, sister chromatid exchange), Micronucleus (MN) frequency in mono and binucleated cells (MN with condensed chromatin, lobed nucleus, nuclear buds, mitotic index, nucleoplasmatic bridges, pyknosis, and karyorrhexis), comet assay (tail intensity, tail length, tail moment, and olive tail moment), and oxidative DNA damage (8-hydroxy-deoxyguanosine). Mean differences or standardized mean differences were pooled using a random-effects model. The Cochran- test and statistic were used to monitor heterogeneity among included studies. Twenty-nine studies with 3080 occupationally Cd-exposed and 1807 unexposed workers were included in the review. Cd among the exposed group was higher in blood [4.77 μg/L (-4.94-14.48)] and urine samples [standardized mean difference 0.47 (0.10-0.85)] than in the exposed group. The Cd exposure is positively associated with higher levels of DNA damage characterized by increased frequency of MN [7.35 (-0.32-15.02)], sister chromatid exchange [20.30 (4.34-36.26)], chromosomal aberrations, and oxidative DNA damage (comet assay and 8OHdG [0.41 (0.20-0.63)]) compared to the unexposed. However, with considerable between-study heterogeneity. Chronic Cd exposure is associated with augmented DNA damage. However, more extensive longitudinal studies with adequate sample sizes are necessary to assist the current observations and promote comprehension of the Cd's role in inducing DNA damage. CRD42022348874.

摘要

现有文献表明,长期接触镉(Cd)与DNA损伤和遗传毒性的诱导之间存在关联。然而,个别研究的观察结果并不一致且相互矛盾。因此,本次系统评价旨在汇总现有文献中的证据,以综合关于遗传毒性标志物与职业性镉暴露人群之间关联的定量和定性确证。在系统检索文献后,选择了评估职业性镉暴露和未暴露工人DNA损伤标志物的研究。纳入的DNA损伤标志物包括染色体畸变(染色体、染色单体、姐妹染色单体交换)、单核和双核细胞中的微核(MN)频率(具有浓缩染色质、叶状核、核芽、有丝分裂指数、核质桥、固缩和核溶解的MN)、彗星试验(尾强度、尾长度、尾矩和橄榄尾矩)以及氧化性DNA损伤(8-羟基脱氧鸟苷)。使用随机效应模型汇总平均差异或标准化平均差异。采用Cochran检验和I²统计量监测纳入研究之间的异质性。该评价纳入了29项研究,涉及3080名职业性镉暴露工人和1807名未暴露工人。暴露组血液中的镉[4.77μg/L(-4.94 - 14.48)]和尿液样本中的镉[标准化平均差异0.47(0.10 - 0.85)]高于未暴露组。与未暴露组相比,镉暴露与更高水平的DNA损伤呈正相关,表现为MN频率增加[7.35(-0.32 - 15.02)]、姐妹染色单体交换增加[20.30(4.34 - 36.26)]、染色体畸变以及氧化性DNA损伤(彗星试验和8-OHdG[0.41(0.20 - 0.63)])。然而,研究之间存在相当大的异质性。长期镉暴露与DNA损伤增加有关。然而,需要更广泛的纵向研究和足够的样本量来支持当前的观察结果,并促进对镉在诱导DNA损伤中作用的理解。CRD42022348874。

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