5-, 7-和9-羟基-2-硝基芴的肿瘤前病变,DNA加合物的形成和致突变性,空气污染物2-硝基芴的代谢物

Xian-Shu Cui , Jan Bergman , Lennart Möller
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引用次数: 32

摘要

比较了2-硝基芴(NF)、5-、7-和9- oh -2-硝基芴(OH-NF)代谢物的遗传毒性。大鼠腹腔单独给药(100 mg/kg体重量)72小时后,采用32P-TLC和32P-HPLC分析肝组织DNA加合物。一个体内肝脏模型被用来测试上述物质对肿瘤前病变形成的启动能力。5-OH-NF诱导DNA加合物形成的能力较低,作为引发大鼠肝脏肿瘤前病变-灶/结节的潜力较低。7-和9-OH-NF均可诱导DNA加合物和肿瘤前肝脏病变,但与NF相比,其数量较少。7-和9-OH-NF似乎不能被认为是NF的解毒产物。总的来说,这些物质对肿瘤前病变形成的启动能力与其形成DNA加合物的能力有很好的相关性。
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Preneoplastic lesions, DNA adduct formation and mutagenicity of 5-, 7- and 9-hydroxy-2-nitrofluorene, metabolites of the air pollutant 2-nitrofluorene

The metabolites of 2-nitrofluorene (NF), 5-, 7- and 9-OH-2-nitrofluorene (OH-NF) were compared for their genotoxicity. Seventy-two hours after intraperitoneal administration of these substances individually to rats (100 mg/kg body wt.), DNA adducts in liver tissue were analyzed with 32P-TLC and 32P-HPLC. An in vivo liver model was used to test the initiating capacity of the said substances for the formation of preneoplastic lesions. 5-OH-NF showed low capacity to induced DNA adduct formation and low potential as initiator to induce preneoplastic lesions-foci/nodules in the liver of rats. Both 7- and 9-OH-NF induced DNA adducts and preneoplastic liver lesions but with smaller quantities compared to NF. It seems that 7- and 9-OH-NF can not be considered as detoxification products of NF. In general, the initiating capacity of these substances for the formation of preneoplastic lesions has a good correlation with their potency to form DNA adducts.

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