Effects of polycyclic aromatic hydrocarbons and multiple metals co-exposure on the mosaic loss of chromosome Y in peripheral blood
Effects of polycyclic aromatic hydrocarbons and multiple metals co-exposure on the mosaic loss of chromosome Y in peripheral blood
复制标题
多环芳烃与多种金属共暴露对外周血Y染色体马赛克丢失的影响
DOI：
10.1016/j.jhazmat.2021.125519
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发表时间：
2021-03-03
影响因子：
13.6
通讯作者：
Guo, Huan
中科院分区：
文献类型：
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作者：
Bai, Yansen;Guan, Xin;Guo, Huan
染色体Y（MLOY）的镶嵌性损失是基因组不稳定性的指标，但MLOY的环境压力源仍然很大未知。在这项研究中，我们检测到888名焦炭工人中11个多环芳烃（PAH）代谢物的内部暴露水平和22个金属的内部暴露水平，并根据全基因组SNP基因分型数据计算了其血液MLOY，并作为中间log Ratio（MLRRR-Y）表示。通用线性模型（GLM），Lasso和贝叶斯内核机回归（BKMR）用于选择与MLOY相关的化学物质。这些模型的结果一致地表明，尿尿1-羟基萘（1-OHNA），锑（SB）和molybdenum（MO）与MLRR-Y的负剂量反应关系。 There were no pairwise interactions between these three chemicals (Pinteraction > 0.05), but subjects with high exposure to >= 2 kinds of these chemicals showed reducing mLRR-Y [13(95%CI) = - 0.015(- 0.023, - 0.008)], increasing oxidative DNA damage (marked by 8-hydroxydeoxyguanosine) [13(95%CI) = 0.625（0.454，0.796）]和染色体损伤（淋巴细胞中的微核频率为标记）[频率比（FR）和95％CI = 1.146（1.047，1.225）比低暴露于所有这些化学物质的人。 1-OHNA，SB和MO对升高DNA损伤的综合作用可能部分解释了它们对增加血液MLOY的关节作用。这些结果为环境危害在染色体上的缺失中的共同暴露提供了新的见解。
Mosaic loss of chromosome Y (mLOY) is an indicator of genome instability, but the environmental stressors of mLOY remained largely unknown. In this study, we detected the internal exposure levels of 11 polycyclic aromatic hydrocarbon (PAH) metabolites and 22 metals among 888 coke-oven workers, and calculated their blood mLOY based on genome-wide SNP genotyping data and presented as median log R ratio (mLRR-Y). The generalized linear model (GLM), LASSO, and Bayesian kernel machine regression (BKMR), were used to select mLOY-relevant chemicals. The results of these models consistently suggested the negative dose-response relationships of urinary 1-hydroxynaphthalene (1-OHNa), antimony (Sb), and molybdenum (Mo) with mLRR-Y. There were no pairwise interactions between these three chemicals (Pinteraction > 0.05), but subjects with high exposure to >= 2 kinds of these chemicals showed reducing mLRR-Y [13(95%CI) = - 0.015(- 0.023, - 0.008)], increasing oxidative DNA damage (marked by 8-hydroxydeoxyguanosine) [13(95%CI) = 0.625(0.454, 0.796)] and chromosome damage (marked by micronucleus frequency in lymphocytes) [frequency ratio (FR) and 95%CI =1.146(1.047, 1.225)] than those with low exposure to all these chemicals. The combined effects of 1-OHNa, Sb, and Mo on elevating DNA damage may partly explain their joint effects on increased blood mLOY. These results provided a new insight into environmental hazards co-exposure on chromosome-Y deletions.