CYP1A1 and CYP1B1 gene expression and DNA adduct formation in normal human mammary epithelial cells exposed to benzo[a]pyrene in the absence or presence of chlorophyllin.
CYP1A1 and CYP1B1 gene expression and DNA adduct formation in normal human mammary epithelial cells exposed to benzo[a]pyrene in the absence or presence of chlorophyllin.
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在不存在或存在叶绿素的情况下，在正常的人类乳腺上皮细胞中，正常的人类乳腺上皮细胞中的CYP1A1和CYP1B1基因表达和DNA加合物形成。
DOI：
10.1016/j.canlet.2009.12.008
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发表时间：
2010-06-28
期刊：
影响因子：
9.7
通讯作者：
Weston, Ainsley
中科院分区：
文献类型：
--
作者：
John, Kaarthik;Divi, Rao L.;Keshava, Channa;Orozco, Christine C.;Schockley, Marie E.;Richardson, Diana L.;Poirier, Miriam C.;Nath, Joginder;Weston, Ainsley
关键词：
苯并[a]芘（BP）是一种强致癌物和普遍存在的环境污染物。本文研究了20株原代正常人乳腺上皮细胞（NHMEC）暴露于BP （4 μM）环境中，在叶绿素（5 μM）缺失或存在的情况下，CYP1A1、CYP1B1和10-（脱氧鸟苷- n2 -基）-7,8,9-三羟基-7,8,9,10-四氢苯并[a]芘（BPdG）加合物形成的诱导和调节。实时聚合酶链反应（RT-PCR）分析显示，BP对CYP1A1和CYP1B1均有很强的诱导作用，且具有较高的个体间差异。采用r7,18 -二羟基-t- 9,10环氧-7,8,9,10-四氢苯并[a]芘(BPDE)-DNA化学发光法（CIA）检测所有菌株的BPdG生成均有变化。叶绿素减轻了BP诱导的所有20个菌株的CYP1A1和CYP1B1基因表达。在bp暴露前给予叶绿素，可降低18/20株NHMEC菌株CYP1A1表达（p < 0.005）和17/20株NHMEC菌株CYP1B1表达（p < 0.005）。当细胞预先给药叶绿素后再给药叶绿素时，观察到CYP1A1和CYP1B1基因表达和BPdG加合物形成的最大百分比降低（CYP1A1和CYP1B1表达p < 0.005， BPdG加合物p < 0.0005）。因此，叶绿素很可能是一种很好的化学保护剂，适用于大部分人群。
Benzo[a]pyrene (BP) is a potent pro-carcinogen and ubiquitous environmental pollutant. Here, we examined the induction and modulation of CYP1A1 and CYP1B1 and 10-(deoxyguanosin-N2-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG) adduct formation in DNA from 20 primary normal human mammary epithelial cell (NHMEC) strains exposed to BP (4 μM) in the absence or presence of chlorophyllin (5 μM). Real-time polymerase chain reaction (RT-PCR) analysis revealed strong induction of both CYP1A1 and CYP1B1 by BP, with high levels of inter-individual variability. Variable BPdG formation was found in all strains by r7, t8-dihydroxy-t-9, 10 epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE)-DNA chemiluminescence assay (CIA). Chlorophyllin mitigated BP-induced CYP1A1 and CYP1B1 gene expression in all 20 strains when administered with BP. Chlorophyllin, administered prior to BP-exposure, mitigated CYP1A1 expression in 18/20 NHMEC strains (p < 0.005) and CYP1B1 expression in 17/20 NHMEC strains (p < 0.005). Maximum percent reductions of CYP1A1 and CYP1B1 gene expression and BPdG adduct formation were observed when cells were pre-dosed with chlorophyllin followed by administration of the carcinogen with chlorophyllin (p < 0.005 for CYP1A1 and CYP1B1 expression and p < 0.0005 for BPdG adducts). Therefore, chlorophyllin is likely to be a good chemoprotective agent for a large proportion of the human population.
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