Analysis On The Effect And Mechanisms Of Estrogen's Enhancement On Carcinogenesis Of B[a]P In Mice

Objective:Currently,the lung cancer is a malignant tumor with the highest incidence and mortality in the whole world.The incidence of women lung cancer keeps on increasing and there is a higher incidence of women than men with the same condition of equal quantity and time of cigarette in the current epidemiological investigation.But all those statistical results haven't been confirmed by the animal model and the mechanisms are unclear,either.This study has established the mice lung cancer mode induced by benzo[a]pyrene(B[a]P),and investigated the effect and mechanisms of estrogen in this animal model.Methods:1.By oraled the B[a]P and injected estrogen or Tamoxifen subcutaneously,a lung cancer and intervention model of femal KunMing mice was established.2.The levels of serum reactive oxygen species(ROS),total superoxide dismutase (T-SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-PX) and E2 were detected by ELASA kids.3.The expression of related proteins and genes of the mitochondrial apoptosis pathway in mice lung tissue were investigated by Western Blotting and real-time PCR.Result and conclusions:1.A lung cancer model induced by B[a]P and intervened by estrogen or Tamoxifen of femal KunMing mice has been established successfully for the first time in our state.The results show compared with the group of control,the lung tumor multiplicity and tumor incidence of the group which treated with B[a]P were higher,and indicate B[a]P is carcinogenesis;The group of B[a]P combined with E2 is higher than the other groups significantly,then indicate the promotion effection of E2 during B[a]P induce cancer;The tumor incidence of the B[a]P combined with E2 and TAM group is higher than control group,but it is lower than B[a]P combined with E2 group,so this result indicate TAM can inhibit the promotion effection of E2 during B[a]P induce cancer.The tumor incidence of TAM group isn't different from it in the control group.2.The groups with high tumor incidence have higher levels of ROS and MDA in the serum,and the level of SOD and GSH-PX is low in those groups correspondingly.The results indicate the activity of oxidant is increasing and the antioxidant activity is decreasing during the lung cancer induced by B[a]P occurs.3.B[a]P induces the mitochondrial pathway in the mice lung tissue.B[a]P can produce an increase of the level of Bax and Caspase-3 protein and gene,and release of Cytochrome C into cytosolic,but a decline in Bcl-2 gene and the ratio of Bcl-2/Bax.The estrogen has inhibited the effect of B[a]p,and promotes the cell apoptosis;but the effect of Tamoxifen is opposite to promote the apoptosis of cell in the lung tissue.4.Estrogen can enhance the effect of carcinogenesis of B[a]P and tamoxifen can inhibit this enhancement of estrogen.The effect of carcinogenesis of B[a]P and the enhancement of estrogen may invoice the oxidant and antioxidant system and the mitochondria apoptosis pathway.