| It is generally understood in the world that smoking is the major cause of lung cancer, the tumor with the highest incidence and mortality in all malignant tumors. Benzo[a]pyrene (B[a]P) is the major carcinogen of smoking. Epidemiological studies indicated that females may have a higher susceptibility to tobacco smoke carcinogens than males, which might relate to the higher estrogen level in females. However, some experts held different opinions, they believed that the higher susceptibility to lung cancer of females might relate to their long-term exposure to cooking oil fume, which contains carcinogens such as B[a]P. The effect of estrogen in lung carcinogenesis remains to be elusive. In this study, we used a male mouse lung cancer model induced by benzo[a]pyrene to explore the mechanism of B[a]P-induced lung carcinogenesis and the intervention of 17β-Estradiol (E2) from the aspects of oxidant and anti-oxidant and mitochondrial injury.By B[a]p gavage and E2 hypodermic injection, we successfully developed a male KunMing mice lung cancer model and 17β-estradiol intervention model. The lung tumor incidence and multiplicity of the B[a]P group were significantly higher than those of control group and E2 group. The lung tumor incidence and multiplicity of B[a]P+E2 group were lower than those of B[a]P group, with statistical significance in tumor multiplicity. It indicated that E2 reduced the lung tumor multiplicity induced by B[a]P, and inhibited the carcinogenesis of B[a]P.The levels of serum reactive oxygen species (ROS), total superoxide dismutase (T-SOD), malondialdehyde (MDA), glutathione peroxidase(GSH-PX) and E2 were also detected. The increase of ROS content and the reduction of GSH-PX activity consisted with the lung tumor incidence and multiplicity of each group. The increase of MDA content and the reduction of T-SOD activity and E2 concentration consisted with the lung tumor incidence and multiplicity of B[a]P group. We also investigated the expression of related proteins and genes of the mitochondrial apoptosis pathway in mouse lung tissue by Western Blotting and RT-PCR. B[a]P treatment produced an increase in the level of Bax gene and release of Cytochrome C into Cytosolic, but a decline in Bcl-2 protein, Bcl-2 gene and the ratio of Bcl-2/Bax. The effects of B[a]P in mitochondrial apoptosis pathway were inhibited by E2.In conclusion, a male mouse lung cancer model induced by benzo[a]pyrene and 17β-estradiol intervention was successfully developed. B[a]P induced lung carcinogenesis by the way of oxidative stress and mitochondrial injury while E2 inhibited the effects of B[a]P. |
