Sulfur dioxide and benzo(a)pyrene modulates CYP1A and tumor‐related gene expression in rat liver
Sulfur dioxide and benzo(a)pyrene modulates CYP1A and tumor‐related gene expression in rat liver
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DOI：
10.1002/tox.20484
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发表时间：
2009-04
影响因子：
4.5
通讯作者：
Guohua Qin;Z. Meng
中科院分区：
文献类型：
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作者：
Guohua Qin;Z. Meng
二氧化硫（SO2）和苯并（a）芘（B（a）P）是常见的工业和环境污染物。然而，关于SO2对原癌基因和肿瘤抑制基因的影响，以及SO2与其他调节原癌基因或肿瘤抑制基因表达的外源性物质之间的相互作用的数据很少。为探讨SO_2与B（a）P的相互作用，雄性Wistar大鼠分别经气管内滴入SO_2和B（a）P，并同时吸入SO_2。我们检测了肝脏中CYP 1A 1和1A 2的mRNA表达、7-乙氧基试卤灵O-脱乙基酶（EROD）和甲氧基试卤灵O-脱甲基酶（MROD）活性。分别通过真实的实时RT-PCR和Western blot分析肝脏中几种癌症相关基因的mRNA和蛋白水平。SO2可下调EROD/MROD活性和CYP 1A 1/2表达，而单独给予B（a）P则可上调EROD/MROD活性和CYP 1A 1/2表达。SO2单独暴露诱导c-fos、c-jun、c-myc、H-ras和p53表达，并抑制肝脏中p16和Rb的表达。B（a）P对上述基因的影响除c‐fos表达外与SO2相似。此外，与单独暴露于SO2或B（a）P相比，SO2 + B（a）P暴露增加了肝脏中c-fos、c-jun、c-myc和p53的表达，降低了p16和Rb的表达。然而，在SO2 + B（a）P暴露后，未观察到对H‐ras和CYP 1A 1/2的协同作用。我们的研究结果表明，多种细胞周期调控蛋白在SO2和B（a）P的肝脏毒性中起关键作用。它可能涉及c-fos，c-jun，c-myc和p53的激活。p16-Rb通路可能也参与了这一过程。虽然我们研究的基因产物被归类为癌基因和肿瘤抑制基因，但它们的功能实际上与控制细胞增殖、存活和/或凋亡的更一般过程有关。© 2009 Wiley Periodicals，Inc.环境毒理学，2010年。
Sulfur dioxide (SO2) and benzo(a)pyrene (B(a)P) are common industrial and environmental contaminants. However, few data are available on the effects of SO2 on proto‐oncogenes and tumor suppressor genes, as well as the interactions between SO2 and other xenobiotics regulating proto‐oncogenes or tumor suppressor genes expression. To investigate the interactions between SO2 and B(a)P, male Wistar rats were exposed to intratracheally instilled with B(a)P or SO2 inhalation alone or together. We detected mRNA expression of CYP1A1 and 1A2, 7‐ethoxyresorufin O‐deethylase (EROD), and methoxyresorufin O‐demethylase (MROD) activities in livers. The mRNA and protein levels of several cancer‐related genes were analyzed in livers by real‐time RT‐PCR and Western blot, respectively. The EROD/MROD activities and CYP1A1/2 expression were down‐regulated by SO2 but up‐regulated by B(a)P alone. Exposure of SO2 alone induced c‐fos, c‐jun, c‐myc, H‐ras, and p53 expression, and depressed p16 and Rb expression in livers. The effects of B(a)P on the above gene were similar to SO2 except c‐fos expression. Furthermore, SO2 + B(a)P exposure increased the expression of c‐fos, c‐jun, c‐myc, and p53, and decreased p16 and Rb expression in livers compared with exposed to SO2 or B(a)P alone. However, no synergistic effects were observed on H‐ras and CYP1A1/2 after SO2 + B(a)P exposure. Our findings indicate that multiple cell cycle regulatory proteins play key roles in the toxicity of SO2 and B(a)P in livers. It might involve the activation of c‐fos, c‐jun, c‐myc, and p53. And p16‐Rb pathway might also participate in the progress. Although the gene products we studied are classed as oncogenes and tumor suppressor genes, their functions actually relate to more general processes of control of cell proliferation, survival, and/or apoptosis. © 2009 Wiley Periodicals, Inc. Environ Toxicol, 2010.