• 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • Arsenic is an endocrine disruptor


    Arsenic is an endocrine disruptor with estrogenic activity. Further study has shown that arsenic exposure can significantly increase the expression of estrogen receptor-related genes, steroid metabolism-related enzymes and lung cancer-related genes in the lung tissues of female mice on the occurrence of lung adenocarcinoma in female mice induced by arsenic (Shen et al., 2007). The main purpose of this study is to investigate the accumulation level of arsenic in mice lung tissue and the changes in the expression of ERβ, ERK1/2 and NF-κB in AECII under arsenic (an environmental estrogen carcinogen) exposure. In addition, the effects of arsenic on ERβ and signal transduction pathway-related indexes, which included ERK1/2, NF-κB and BP50/p65, were observed after estrogen receptor antagonist pretreatment, and the mechanism of gender difference in arsenic-induced lung cancer is preliminary explored.
    Materials and methods
    Discussion Endocrine disruptors influence the transmission of hormone signals in cells, tissues and organs mainly by binding ligands by simulating natural hormones or by inhibiting the binding of natural hormones and ligands (Sonnenschein and Soto, 1998), thus resulting in dysfunction of the body. Zhao et al. (2011) found that the over-expression of ERβ promoted the development of non-small cell lung cancer and that the inhibition of SiRNA on ERβ gene could inhibit the growth of cancer Zoniporide dihydrochloride sale and induce their apoptosis. As an environmental estrogen substance, arsenic may enhance the expression of ERβ and interfere with ER signal pathway by combining with ERβ receptor to form arsenic-ERβ complex, therefore affecting the development of lung cancer. Results from this study showed that no significant difference in the expression of ERβ mRNA and protein was observed between the female and the male control groups under different doses of arsenic exposure. In the absence of sodium arsenite exposure, the expression of ERβ in AECII cells in female and male fetal mice was consistent. After arsenic exposure, the expression level of ERβ mRNA increased in female mice in each dose group, and it was higher in female mice in middle and high dose groups than that in male mice in the same dose groups. The results of ERβ protein data were in accordance with the overall trend of mRNA expression. ERβ protein expression in female mice in middle and high dose groups was higher than that in the controls and that in male mice in the same dose group. This indicates that AECII cells in female fetal mice are more sensitive to arsenic, an estrogen-like environmental carcinogen, than those in male fetal mice. Tokar et al. (2011) performed a carcinogenic experiment on arsenic exposure in the whole life period of CD1 mice in 2011. The incidence of adenoma and adenocarcinoma in the female mice was dose-dependent, and the difference was significant between arsenic exposure group and the control group. But no significant difference was found in both of them in male mice. Result from cell test in this study demonstrated that ERβ mRNA and protein expression in male mice in each dose group was not significantly different from that in the control. This result coincides with that of the above animal carcinogenic experiment. This study also showed that the expression level of ERβ mRNA and protein in female mice exposed to both arsenic and ICI182780 (estrogen receptor antagonist) was lower than that in arsenic exposure group, indicating that ICI182780 blocks the up-regulation of ERβ gene and protein in AECII of female fetal mice caused by arsenic, and further determining the effect of ERβ in this regulation procedure. But no significant difference was observed in this expression in male mice between in only arsenic exposure group and combined exposure group (arsenic and ICI182780). This may be associated with delayed toxic effect of arsenic on male AECII cells or resulted from insensitivity of male AECII cells to arsenic or metabolic mechanism of their cells. The detailed cause for this is needed to be explored. In addition, no significant difference was found in expression level of ERβ mRNA and protein in male mice between in each arsenic exposure group and in the control. The results of early cell experiment Zoniporide dihydrochloride sale showed that the expression level of ERα mRNA and protein in male AECII cells in arsenic exposure group was higher than that in the control after their exposure to arsenic for 24 h (Xiong et al., 2017). It might be that arsenic specifically induced the expression level of ERα and ERβ and changed their intracellular distribution, thus altering the biological effects of the estrogen signal pathway mediated by ERα and ERβ, and finally causing different expression levels of these two receptors in male AECII cells. More and more evidences have also proved that the effect of estrogen is not mediated by a subtype receptor, but is a balance between the mediating action of ERα and ERβ (Nemenoff and Winn, 2005).