The potent carcinogen dibenzo[a,l]pyrene is metabolically activated to fjord-region 11,12-diol 13,14-epoxides in human mammary carcinoma MCF-7 cell cultures.
The potent carcinogen dibenzo[a,l]pyrene is metabolically activated to fjord-region 11,12-diol 13,14-epoxides in human mammary carcinoma MCF-7 cell cultures.
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发表时间：
1994-02
期刊：
影响因子：
11.2
通讯作者：
Sherry L. Ralston;H. Lau;Albrecht Seidel;Andreas Luch;Karl L. Platt;William M. Baird
中科院分区：
文献类型：
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作者：
Sherry L. Ralston;H. Lau;Albrecht Seidel;Andreas Luch;Karl L. Platt;William M. Baird
二苯并[a,l]芘 (DB[a,l]P) 是一种环境碳氢化合物，在啮齿动物生物测定中是一种强效致癌物，可通过形成三种不同的区域异构体湾区或峡湾区二醇环氧化物或其他高度氧化的代谢物，在细胞中被激活为 DNA 结合中间体。通过分析[35S]硫代磷酸酯后标记、固定化硼酸盐色谱和高效液相色谱形成的DB[a,l]P-DNA加合物，阐明了人乳腺癌细胞系MCF-7中DB[a,l]P的代谢激活机制。检测到六种 DB[a,l]P-DNA 加合物。与细胞中 DB[a,l]P-11,12-二醇以及 DNA 与顺式和抗式（分别为顺式和反式苯甲基羟基和环氧化物氧）DB[a,l]P-11,12-二醇-13,14-环氧化物 (DB[a,l]PDE) 反应形成的比较表明，MCF-7 细胞中的所有 DB[a,l]P-DNA 加合物都是由这些二醇-环氧化物形成的异构体。细胞DNA含有大量的两种顺式和一种抗式DB[a,l]PDE-DNA加合物以及少量的一种顺式和两种抗式DB[a,l]PDE-DNA加合物。人类细胞将 DB-[a,l]P 激活其峡湾区域 11,12-二醇 13,14-环氧化物的能力表明，环境中暴露于 DB[a,l]P 可能对人类构成风险。
Dibenzo[a,l]pyrene (DB[a,l]P), an environmental hydrocarbon and very potent carcinogen in rodent bioassays, could be activated to DNA-binding intermediates in cells through formation of three different regioisomeric bay- or fjord-region diol-epoxides or other more highly oxidized metabolites. The mechanism of metabolic activation of DB[a,l]P in the human mammary carcinoma cell line MCF-7 was elucidated by analyzing the DB[a,l]P-DNA adducts formed by [35S]phosphorothioate postlabeling, immobilized boronate chromatography, and high-performance liquid chromatography. Six DB[a,l]P-DNA adducts were detected. Comparison with those formed in cells by DB[a,l]P-11,12-diol and by reaction of DNA with syn- and anti-(benzylic hydroxyl and epoxide oxygen cis and trans, respectively) DB[a,l]P-11,12-diol-13,14-epoxide (DB[a,l]PDE) demonstrated that all DB[a,l]P-DNA adducts in MCF-7 cells were formed by these diol-epoxide isomers. Cellular DNA contained large amounts of two syn- and one anti-DB[a,l]PDE-DNA adducts and small amounts of one syn- and two anti-DB[a,l]PDE-DNA adducts. The ability of human cells to activate DB-[a,l]P to its fjord-region 11,12-diol 13,14-epoxides suggests that environmental exposure to DB[a,l]P could pose a risk for humans.