背景:苯并(a)芘(B[a]P)是最受关注的多环芳烃(PAHs),在体内代谢苯并(a)芘-7,8-二氢二醇-9,10-环氧化物(BPDE)以对人体产生致癌作用。目前,关于代谢酶变化在这一过程中的作用的研究有限。
方法:我们进行了一项包括752名参与者的研究,测量了颗粒相和气相中16种PAHs的浓度,尿PAHs代谢物,白细胞BPDE-DNA加合物和血清BPDE-白蛋白(BPDE-Alb)加合物,并计算每日摄入剂量(DID)以评估PAHs的累积暴露。我们进行了代谢酶的单核苷酸多态性位点(SNP),使用多元线性回归模型探索暴露水平与BPDE加合物之间的暴露-反应关系。
结果:我们的结果表明,B[a]P的四分位数间距(IQR)增加,PAHs,BaPeq,1-羟基芘(1-OHP),1-羟基萘(1-OHNap)和2-羟基萘(2-OHNap)与26.53%,24.24%,28.15%,39.15%,白细胞BPDE-DNA加合物增加12.85%和14.09%(均P<0.05)。然而,暴露与血清BPDE-Alb加合物无显著相关性(P>0.05)。此外,我们还发现CYP1A1(Gly45Asp)的多态性,CYP2C9(Ile359Leu),和UGT1A1(下游)可能会影响BPDE加合物水平。
结论:我们的结果表明白细胞BPDE-DNA加合物可以更好地反映PAHs的暴露。此外,CYP1A1,CYP2C9和UGT1A1的多态性影响了BPDE加合物的含量。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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(Gly45Asp), CYP2C9 (Ile359Leu), and UGT1A1(downstream) may affect BPDE adducts level.
CONCLUSIONS: 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.