213 DIOXIN SIGNIFICANTLY ENHANCED THE TUMOR MASS FORMATION IN A XENOGRAFTED MOUSE MODEL TRANSPLANTED WITH BG-1 OVARIAN CANCER CELLS

Abstract

Previous studies suggest that environmental factors, such as high levels of meat consumption, caffeine, cigarette smoking, and endocrine disrupting chemicals (EDC), may enhance a high risk of ovarian cancer. Cytochrome P450 (CYP) 1A1 may play a major role in metabolic activation of procarcinogens to carcinogens. For example, polycyclic aromatic hydrocarbons (PAHs) and halogenated aromatic hydrocarbons (HAHs) occur by pyrolysis of fossil fuels and flow into the body by organic matter, such as tobacco leaves and contaminated water by pesticides. 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD) is a commonplace pollutant and promoter of carcinogenesis as the most potent substance. In this study, we examined the effects of 17β-oestradiol (E2), TCDD, and TCDD in the presence of E2 on the expressions of CYP1A1, CYP1B1, and aryl hydrocarbon receptor (AhR) by RT–PCR analysis and Western blot analysis. In addition, the cell viability by TCDD and E2 were examined in BG-1 human ovarian cancer cells by MTT assay. To evaluate the cell viability, BG-1 cells were cultured with a negative control (0.1% DMSO), E2 (1 × 10^–9 M) or TCDD (10^–6–10^–8 M). E2 markedly increased BG-1 cell viability ~5 times, and TCDD also induced BG-1 cell viability highest at the concentration of 1 × 10^–8 M compared to a control (0.1% DMSO) (P < 0.05). When respective treatment was co-treated with ICI 182 780, an ER antagonist, BG-1 cell viability was reversed to the level of a negative control. Although the mRNA expression of CYP1B1 was not altered by E2, TCDD, or TCDD plus E2, the transcriptional level of CYP1A1 appeared to be increased by E2 and TCDD in a time-dependent manner. When the cells were treated with TCDD plus E2, the mRNA level of CYP1A1 was more greatly increased than by only TCDD or E2 treatment. In xenograft mouse models transplanted with BG-1 cells, E2 treatment significantly increased the tumour mass formation ~6 times, and TCDD also induced tumour formation ~4 times compared to a vehicle (0.1% DMSO in PBS) during 8 weeks in this xenograted mouse model. In addition, TCDD plus E2 treatment also greatly induced ovarian tumour formation compared to only E2 treatment in this mouse model. Taken together, these results indicate that TCDD may induce ovarian cancer cell growth via CYP1A1 gene expression and have disruptive effect in oestrogen receptor (ER) expressing cells or tissues.