Objective: To determine the effects of arsenic and estrogen receptor antagonist (ICI182, 780) on the expression of estrogen receptor beta (ERβ) in alveolar Ⅱ epithelial cells (AECⅡ) of female and male mice.
Methods: Nineteen or twenty day fetus mice were obtained through caesarean section of ICR mice. Purified AECⅡ cells were separated from the female and male fetus,respectively,and confirmed using immunofluorescence staining. The cells were exposed to sodium arsenite (NaAsO) at a low,medium,or high dosage determined by MTT and cultured for 24 h. The NaAsO (5 μmol/L) exposed cells were compared with those treated (for 24 h) with dimethyl sulfoxide (DMSO) or ICI182, 780 (1×10 mol/L). Apoptosis rates of the cells were measured by flow cytometry. Real-time fluorescence quantitative PCR method and Western blot technique were used to detect the expression ofmRNA and protein in AECⅡ.
Results: Purity of AECⅡ cells reached (87.0±2.5)%. NaAsO exposure was set at a concentration of 0.5 (low),1.25 (medium),and 5 (high) μmol/L. The cells exposed to medium and high dosage of NaAsO had higher apoptosis rates than the blank controls (<0.05),without sex differences. Female cells exposed to medium and high dosage of NaAsO had higher levels of expressions ofmRNA and protein than the blank controls (<0.05) and male cells exposed to the same dosage of NaAsO (<0.05). No significant differences were found in the expressions ofmRNA and protein between the exposed male cells and the blank controls. ICI182, 780 lowered the expression levels ofmRNA and protein in the female exposed cells (<0.01).
Conclusion: Arsenic exposure increases expressions of AECⅡ's ERβ,more so in female cells than in male cells. This can be blocked by estrogen receptor antagonists.
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Breast Cancer Res
January 2025
College of Pharmacy, Seoul National University, Seoul, 08826, South Korea.
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