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Sulfur dioxide and benzo(a)pyrene modulates CYP1A and tumor‐related gene expression in rat liver
AbstractSulfur dioxide (SO2) and benzo(a)pyrene (B(a)P) are common industrial and environmental contaminants. However, few data are available on the effects of SO2on proto‐oncogenes and tumor suppressor genes, as well as the interactions between SO2and other xenobiotics regulating proto‐oncogenes or tumor suppressor genes expression. To investigate the interactions between SO2and B(a)P, male Wistar rats were exposed to intratracheally instilled with B(a)P or SO2inhalation alone or together. We detected mRNA expression ofCYP1A1and1A2, 7‐ethoxyresorufinO‐deethylase (EROD), and methoxyresorufinO‐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 andCYP1A1/2expression were down‐regulated by SO2but up‐regulated by B(a)P alone. Exposure of SO2alone 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 SO2except 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 SO2or 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 SO2and 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.
Sulfur dioxide and benzo(a)pyrene modulates CYP1A and tumor‐related gene expression in rat liver
AbstractSulfur dioxide (SO2) and benzo(a)pyrene (B(a)P) are common industrial and environmental contaminants. However, few data are available on the effects of SO2on proto‐oncogenes and tumor suppressor genes, as well as the interactions between SO2and other xenobiotics regulating proto‐oncogenes or tumor suppressor genes expression. To investigate the interactions between SO2and B(a)P, male Wistar rats were exposed to intratracheally instilled with B(a)P or SO2inhalation alone or together. We detected mRNA expression ofCYP1A1and1A2, 7‐ethoxyresorufinO‐deethylase (EROD), and methoxyresorufinO‐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 andCYP1A1/2expression were down‐regulated by SO2but up‐regulated by B(a)P alone. Exposure of SO2alone 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 SO2except 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 SO2or 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 SO2and 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.
Sulfur dioxide and benzo(a)pyrene modulates CYP1A and tumor‐related gene expression in rat liver
Environmental Toxicology
Qin, Guohua (author) / Meng, Ziqiang (author)
Environmental Toxicology ; 25 ; 169-179
2010-04-01
Article (Journal)
Electronic Resource
English
Sulfur dioxide and benzo(a)pyrene modulates CYP1A and tumor-related gene expression in rat liver
| Online Contents | 2010