Third-hand smoke exposure is associated with abnormal serum melatonin level via hypomethylation of CYP1A2 promoter: Evidence from human and animal studies.

Wenbo Jiang, Huanyu Wu, Xinyang Yu, Yu Wang, Wenbo Gu, Wei Wei, Bai Li, XiTao Jiang, Yue Wang, Wanying Hou, Qiuying Dong, Xuemin Yan, Ying Li, Changhao Sun, Tianshu Han

Environmental pollution (Barking, Essex : 1987) 2021 May 15

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This study aimed to examine whether and how third-hand smoke (THS) exposure would influence serum melatonin level. 1083 participants with or without exposure to THS were enrolled. Serum ROS, SOD, GSH-Px, and melatonin were measured by ELISA. Methylation microarrays detection and WGCNA were performed to identify hub methylated-sites. The methylation levels of hub-sites were validated in addtional samples. Moreover, mice were exposed to THS for 6 months mimicking exposure of human and the serum, liver, and pineal were collected. Oxidative stress-related indicators in serum, pineal, and liver were measured by ELISA. The expressions of mRNA and protein and methylation levels of hub-gene discovered in human data were further explored by RT-PCR, western-blot, and TBS. The results showed the participants exposed to THS had lower melatonin-level. 820 differentially methylated sites associated with THS were identified. And the hub-site located on the CYP1A2 promoter was identified, which mediated the association between THS and decreased melatonin-level. Decreased peak of serum melatonin, increased ROS and reduced SOD and GSH-Px in pineal and liver, and elevated CYP1A2 expression in liver was also found in the THS-exposed mice. Hypo-methylation of 7 CPG sites on the CYP1A2 promoter was identified, which accelerated the catabolism of melatonin. Overall, THS exposure is associated with abnormal melatonin catabolism through hypo-methylation of CYP1A2-promoter. Copyright © 2021 Elsevier Ltd. All rights reserved.

Citation

Wenbo Jiang, Huanyu Wu, Xinyang Yu, Yu Wang, Wenbo Gu, Wei Wei, Bai Li, XiTao Jiang, Yue Wang, Wanying Hou, Qiuying Dong, Xuemin Yan, Ying Li, Changhao Sun, Tianshu Han. Third-hand smoke exposure is associated with abnormal serum melatonin level via hypomethylation of CYP1A2 promoter: Evidence from human and animal studies. Environmental pollution (Barking, Essex : 1987). 2021 May 15;277:116669