Environmental factors such as high meat consumption, caffeine, cigarette smoking, and endocrine disrupting chemical (EDCs) may enhance the risk of ovarian cancer. Cytochrome P450 (CYP) 1A1 may play a major role in metabolic activation of procarcinogens to carcinogens. 2,3,7,8-Tetrachlorodibenzo-ρ-dioxin (TCDD) is a commonplace pollutant and a promoter of carcinogenesis as the most potent substance. In this study, we examined the effects of TCDD in the presence of 17β-estradiol (E2) on the expressions of CYP1A1, CYP1B1, and aryl hydrocarbon receptor (AhR) by RT-PCR and western blot analysis. In addition, the cell viability by TCDD and E2 was examined in BG-1 human ovarian cancer cells by MTT assay. To evaluate the cell viability, BG-1 cells were cultured with control (0.1% DMSO), E2 (1×10−9 M), or TCDD (10−610−8 M). E2 markedly increased BG-1 cell viability about five times and TCDD also induced BG-1 cell viability the most at 1×10−8 M compared to control. When co-treated with ICI 182 780, an ER antagonist, BG-1 cell viability was reversed to the level of control. Although, mRNA expression of CYP1B1 or AhR was not altered by E2 or TCDD, the transcriptional level of CYP1A1 appeared to be increased by E2 or TCDD in a time-dependent manner. Furthermore the translational level of AhR and CYP1A1 appeared to be increased by E2 or TCDD in a time-dependent manner. In xenografted mouse models transplanted with BG-1 cells, E2 treatment significantly increased the tumour mass formation about six times and TCDD induced tumour formation about four times compared to vehicle (0.1% DMSO) during 80 days. In addition, expression levels of proliferation cell nuclear antigen, AhR and CYP1A1 are increased in E2 or TCDD-treated tumour section compared to the control. Taken together, TCDD may induce ovarian cancer cell growth via CYP1A1 gene expression and have a disruptive effect in ER expressing cells or tissues. This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (MEST) of the Republic of Korea (2014R1A1A2055295).
Disclosure: This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (MEST) of the Republic of Korea (2014R1A1A2055295).