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The Carcinogen (7R,8S)-Dihydroxy-(9S,10R)-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene Induces Cdc25B Expression in Human Bronchial and Lung Cancer Cells¹

Department of Pharmacology, University of Pittsburgh [T. O., S. V. S., K. N., J. S. L.], Pittsburgh, Pennsylvania 15261, and Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan [T. O.]

Cdc25B regulates cell cycle progression and genetic stability. Here, we report that exposure to the environmental carcinogen (7R,8S)-dihydroxy-(9S,10R)-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) causes a marked increase in the expression of Cdc25B mRNA and protein levels in terminal squamous differentiated human bronchial epithelial cells and in lung cancer cells, but not in undifferentiated bronchial cells. In addition, the growth rate of lung cancer cells was increased significantly in comparison with untreated cells after chronic exposure to 0.1 µM anti-BPDE. Furthermore, increased Cdc25B expression and decreased Cdk1 phosphorylation were observed in anti-BPDE-treated cells. We postulate that the induction of Cdc25B expression in lung cancer cells by the ultimate carcinogen anti-BPDE accelerates the further development of lung carcinogenesis.

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