Institute of Urban Safety and Environmental Science, Beijing Academy of Science and Technology, Beijing, China.
State Key Laboratory of Trauma and Chemical Poisoning, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China; Chinese Medical University, Shenyang, Liaoning, China.
Environ Int. 2024 Aug;190:108922. doi: 10.1016/j.envint.2024.108922. Epub 2024 Aug 5.
Benzo(a)pyrene (B[a]P) is the most widely concerned polycyclic aromatic hydrocarbons (PAHs), which metabolizes benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) in vivo to produce carcinogenic effect on the body. Currently, there is limited research on the role of the variation of metabolic enzymes in this process.
We carried out a study including 752 participants, measured the concentrations of 16 kinds PAHs in both particle and gaseous phases, urinary PAHs metabolites, leukocyte BPDE-DNA adduct and serum BPDE- Albumin (BPDE-Alb) adduct, and calculated daily intake dose (DID) to assess the cumulative exposure of PAHs. We conducted single nucleotide polymorphism sites (SNPs) of metabolic enzymes, explored the exposure-response relationship between the levels of exposure and BPDE adducts using multiple linear regression models.
Our results indicated that an interquartile range (IQR) increase in B[a]P, PAHs, BaPeq, 1-hydroxypyrene (1-OHP), 1-hydroxynaphthalene (1-OHNap) and 2-hydroxynaphthalene (2-OHNap) were associated with 26.53 %, 24.24 %, 28.15 %, 39.15 %, 12.85 % and 14.09 % increase in leukocyte BPDE-DNA adduct (all P < 0.05). However, there was no significant correlation between exposure with serum BPDE-Alb adduct (P > 0.05). Besides, we also found the polymorphism of CYP1A1(GlyAsp), CYP2C9 (IleLeu), and UGT1A1(downstream) may affect BPDE adducts level.
Our results indicated that leukocyte BPDE-DNA adduct could better reflect the exposure to PAHs. Furthermore, the polymorphism of CYP1A1, CYP2C9 and UGT1A1affected the content of BPDE adducts.
苯并(a)芘（B[a]P）是最受关注的多环芳烃（PAHs）之一，它在体内将苯并(a)芘-7,8-二氢二醇-9,10-环氧化物（BPDE）代谢为具有致癌作用的物质。目前，关于代谢酶在这一过程中的变异作用的研究有限。
我们进行了一项包含 752 名参与者的研究，测量了颗粒相和气相中 16 种多环芳烃、尿液中多环芳烃代谢物、白细胞 BPDE-DNA 加合物和血清 BPDE-白蛋白（BPDE-Alb）加合物的浓度，并计算了每日摄入量（DID）以评估多环芳烃的累积暴露量。我们检测了代谢酶的单核苷酸多态性（SNP）位点，采用多元线性回归模型探索了暴露水平与 BPDE 加合物之间的暴露反应关系。
我们的研究结果表明，B[a]P、PAHs、BaPeq、1-羟基芘（1-OHP）、1-羟基萘（1-OHNap）和 2-羟基萘（2-OHNap）的四分位距（IQR）每增加一个单位，白细胞 BPDE-DNA 加合物就会分别增加 26.53%、24.24%、28.15%、39.15%、12.85%和 14.09%（均 P<0.05）。然而，血清 BPDE-Alb 加合物与暴露之间没有显著相关性（P>0.05）。此外，我们还发现 CYP1A1（GlyAsp）、CYP2C9（IleLeu）和 UGT1A1（下游）的多态性可能会影响 BPDE 加合物的水平。
我们的研究结果表明，白细胞 BPDE-DNA 加合物能更好地反映多环芳烃的暴露情况。此外，CYP1A1、CYP2C9 和 UGT1A1 的多态性影响 BPDE 加合物的含量。
