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巴西孕妇尿中芳香胺的评估及其与DNA损伤的关联:遗传多样性、生活方式、环境和社会经济因素的影响

Assessment of urinary aromatic amines in Brazilian pregnant women and association with DNA damage: Influence of genetic diversity, lifestyle, and environmental and socioeconomic factors.

作者信息

Souza Marília Cristina Oliveira, González Neus, Rovira Joaquim, Herrero Marta, Marquès Montse, Nadal Martí, Barbosa Fernando, Domingo José Luis

机构信息

University of Sao Paulo, School of Pharmaceutical Sciences of Ribeirao Preto, Department of Clinical Analyses, Toxicology, and Food Sciences (Analytical and System Toxicology Laboratory), Avenida do Café s/n◦, 14040-903, Ribeirao Preto, Sao Paulo, Brazil; Universitat Rovira i Virgili, Laboratory of Toxicology and Environmental Health, School of Medicine, Sant Llorenç 21, 43201, Reus, Catalonia, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), 43204, Reus, Catalonia, Spain.

University of Sao Paulo, School of Pharmaceutical Sciences of Ribeirao Preto, Department of Clinical Analyses, Toxicology, and Food Sciences (Analytical and System Toxicology Laboratory), Avenida do Café s/n◦, 14040-903, Ribeirao Preto, Sao Paulo, Brazil; Universitat Rovira i Virgili, Laboratory of Toxicology and Environmental Health, School of Medicine, Sant Llorenç 21, 43201, Reus, Catalonia, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), 43204, Reus, Catalonia, Spain.

出版信息

Environ Pollut. 2023 Oct 15;335:122366. doi: 10.1016/j.envpol.2023.122366. Epub 2023 Aug 10.

DOI:10.1016/j.envpol.2023.122366
PMID:37572848
Abstract

Aromatic amines (AAs) are polar organic chemicals with a wide environmental distribution originating from various sources, such as tobacco smoke, diesel exhaust, and dermal absorption from textile products with azo dyes. The toxicity profile of AAs is directly related to the amino group's metabolic activation and the generation of the reactive intermediate, forming DNA adducts and potential carcinogenicity. Urinary levels of 8-hydroxy-2'-deoxyguanosine (8OHdG) are an important biomarker of DNA damage. Since AAs have been shown to cross the placental barrier, being a risk factor for adverse birth outcomes, prenatal exposure is a great public health concern. The present study aimed to measure the urinary levels of 58 AAs in Brazilian pregnant women (n = 300) and investigated the impact of this exposure on DNA damage by quantifying 8OHdG levels. The influence of tobacco smoke exposure and dermal absorption of AAs by clothes on urinary levels was also assessed. The results showed a 100% detection rate for eight AAs, two of them regulated by the European Union (2,6-dimethylaniline and 2,4-diaminotolune). Hundreds of AAs may be derived from aniline, which here showed a median of 1.38 ng/mL. Aniline also correlated positively with 2,6-dimethylaniline, p-aminophenol, and other AAs, suggesting exposure to multiple sources. The present findings suggest that both tobacco smoke and dermal contact with clothes containing azo dyes are potential sources that might strongly influence urinary levels of AAs in Brazilian pregnant women. A multiple regression linear model (R = 0.772) suggested that some regulated AAs (i.e., 2-naphthylamine and 4-aminobiphenyl), nicotine, smoke habit, age, and Brazilian region could induce DNA damage occurrence, increasing the levels of 8OHdG. Given the limited available data on human exposure to carcinogenic AAs, as well as the lack of toxicological information on those non-regulated, further studies focused on measuring their levels in human fluids and the potential exposure sources are clearly essential.

摘要

芳香胺(AAs)是极性有机化学品,广泛分布于环境中,其来源多种多样,如烟草烟雾、柴油废气,以及来自含偶氮染料纺织品的皮肤吸收。芳香胺的毒性特征与氨基的代谢活化以及活性中间体的生成直接相关,会形成DNA加合物并具有潜在致癌性。尿中8-羟基-2'-脱氧鸟苷(8OHdG)水平是DNA损伤的重要生物标志物。由于已证明芳香胺可穿过胎盘屏障,是不良出生结局的一个风险因素,因此产前暴露是一个重大的公共卫生问题。本研究旨在测量巴西孕妇(n = 300)尿中58种芳香胺的水平,并通过量化8OHdG水平来研究这种暴露对DNA损伤的影响。还评估了烟草烟雾暴露和衣物对芳香胺的皮肤吸收对尿中水平的影响。结果显示,八种芳香胺的检出率为100%,其中两种受欧盟监管(2,6-二甲基苯胺和2,4-二氨基甲苯)。数百种芳香胺可能源自苯胺,此处苯胺的中位数为1.38 ng/mL。苯胺还与2,6-二甲基苯胺、对氨基酚和其他芳香胺呈正相关,表明存在多种来源的暴露。目前的研究结果表明,烟草烟雾和与含偶氮染料衣物的皮肤接触都是可能强烈影响巴西孕妇尿中芳香胺水平的潜在来源。多元回归线性模型(R = 0.772)表明,一些受监管的芳香胺(即2-萘胺和4-氨基联苯)、尼古丁、吸烟习惯、年龄和巴西地区可能会诱发DNA损伤的发生,增加8OHdG的水平。鉴于关于人类接触致癌芳香胺的现有数据有限,以及缺乏关于那些未受监管的芳香胺的毒理学信息,进一步开展侧重于测量其在人体体液中的水平以及潜在暴露源的研究显然至关重要。

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