Cadmium chloride and sodium arsenate, environmental estrogens in cigarette smoke, activate estrogen signaling pathways to induce proliferation in a human lung adenocarcinoma cell line.

Of the 63 carcinogens in cigarette smoke, cadmium chloride and sodium arsenate are considered environmental estrogens because they mimic the effect of estradiol in living systems. Since recent studies support a role for estrogen in the etiology and progression of lung cancer, we wanted to determine if these environmental estrogens could stimulate cellular proliferation in a similar manner. Treatment of a lung adenocarcinoma cell line NCI-H1793 for 4 days with nanomolar concentrations of cadmium chloride or sodium arsenate induced cellular proliferation similar to that seen for estradiol. These cells express both estrogen receptors alpha and beta. Furthermore, inhibition of the estrogen signaling pathway using an estrogen receptor (ER) antagonist ICI 182,780 partially reduced the observed proliferation. Treatment of H1793 cells transiently transfected with an estrogen response element-driven luciferase reporter gene with estradiol, cadmium chloride or sodium arsenate stimulated luciferase activity in an ER-dependent manner. In addition to this genomic activity, both cadmium chloride and sodium arsenate, like estradiol, stimulated phosphorylation of ERK½ within minutes of treatment. These studies support the involvement of estrogen receptor signaling at both the genomic and non-genomic levels in mediating cellular responses to environmentally relevant concentrations of cadmium chloride and sodium arsenate. [ABSTRACT FROM AUTHOR]