Expression of oncogenes and tumor suppressor genes in lungs of rats exposed to sulfur dioxide and benzo(a)pyrene
Expression of oncogenes and tumor suppressor genes in lungs of rats exposed to sulfur dioxide and benzo(a)pyrene
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二氧化硫和苯并芘暴露大鼠肺中癌基因和抑癌基因的表达
DOI：
10.3109/08958370903341891
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发表时间：
2010-02
影响因子：
2.1
通讯作者：
Meng, Ziqiang
中科院分区：
文献类型：
--
作者：
Qin, Guohua;Meng, Ziqiang
与单独暴露于B（a）P相比，同时暴露于SO2和苯并（a）芘（B（a）P）导致啮齿动物肺肿瘤发病率增加。SO2和B（a）P暴露后，SO2和B（a）P对肺组织c-fos和c-jun的表达具有协同作用。然而，肿瘤发生是通过多个事件发生的，这些事件可能涉及一种以上癌基因的激活以及肿瘤抑制基因的功能丧失。为进一步研究SO2与B（a）P的相互作用，雄性Wistar大鼠经气管内滴注B（a）P（3 mg）或SO2（56 mg/m3），单独或联合染毒。采用实时荧光定量逆转录聚合酶链反应（RT-PCR）和免疫印迹法（Western blot）检测肺组织中癌基因（c-myc和H-ras）和抑癌基因（p53、p16和Rb）的mRNA和蛋白水平。结果表明，各处理均能提高c-myc、H-ras和p53的mRNA和蛋白表达水平，降低p16和Rb的表达水平。一般来说，SO2和B（a）P的组合在影响这些表达水平方面比单独使用任何一种药物更有效，除了H-ras表达。这些结果表明，多种细胞周期调控蛋白在SO2和B（a）P的毒性中起关键作用，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。阐明这些因子在SO2和B（a）P暴露后的表达模式对于理解SO2致癌机制和治疗干预具有重要意义。
Concurrent exposure to SO2 and benzo(a)pyrene (B(a)P) resulted in an increased incidence of lung tumors in rodents compared to exposure to B(a)P alone. A synergistic effect on the expression of c-fos and c-jun between SO2 and B(a)P was observed in lungs after SO2 and B(a)P exposure. However, tumorigenesis occurs by multiple events that may involve the activation of more than one oncogene, as well as the functional loss of the tumor suppressor gene. In order to further investigate the interactions between SO2 and B(a)P, male Wistar rats were exposed via intratracheal instillation of B(a)P (3 mg) or SO2 (56 mg/m3) inhalation, alone or together. The mRNA and protein levels of oncogenes (c-myc and H-ras) and tumor suppressor genes (p53, p16, and Rb) were analyzed in lungs by real-time reverse transcriptase–polymerase chain reaction (RT-PCR) and Western blot, respectively. The results showed that all treatments increased mRNA and protein expression levels of c-myc, H-ras, and p53, and reduced expression levels of p16 and Rb. In general, the combination of SO2 and B(a)P was more effective in influencing these expression levels than either agent alone, except for H-ras expression. These findings indicate that multiple cell cycle regulatory proteins play key roles in the toxicity of SO2 and B(a)P. It might involve the activation of c-fos, c-jun, c-myc, and p53. And the p16-Rb pathway might also participate in the progress. Elucidating the expression patterns of those factors after SO2 and B(a)P exposure may be critical to understanding the mechanisms of SO2 cocarcinogenesis and helpful for therapeutic intervention.
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影响因子：
4.6
作者：
S. Toyokuni
通讯作者：
S. Toyokuni
DOI：
10.1016/s0232-1513(85)80029-3
发表时间：
1985
期刊：
Experimental pathology
影响因子：
--
作者：
J. Pauluhn;J. Thyssen;J. Althoff;G. Kimmerle;U. Mohr
通讯作者：
J. Pauluhn;J. Thyssen;J. Althoff;G. Kimmerle;U. Mohr
影响因子：
3.5
作者：
G. Garçon;P. Gosset;F. Zerimech;B. Grave-Descampiaux;P. Shirali
通讯作者：
G. Garçon;P. Gosset;F. Zerimech;B. Grave-Descampiaux;P. Shirali
DOI：
10.1093/jnci/94.20.1527
发表时间：
2002-10
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Zhaohui Feng;Wenwei Hu;James X. Chen;A. Pao;Haiying Li;W. Rom;M. Hung;M. Tang
通讯作者：
Zhaohui Feng;Wenwei Hu;James X. Chen;A. Pao;Haiying Li;W. Rom;M. Hung;M. Tang
影响因子：
10.4
作者：
Perera F
通讯作者：
Perera F