EFFECT OF A TOBACCO-RELATED NITROSAMINE ON INTERCELLULAR COMMUNICATION IN HUMAN UROTHELIAL CELLS - A POSSIBLE FACTOR IN SMOKING-RELATED BLADDER CARCINOGENESIS

Bladder cancer is associated with smoking. Among the tobacco-derived c arcinogens suspected of being involved in initiating the disease are n itrosamines found in urine. In this study a nitrosamine found in the u rine of smokers was tested using a tissue culture model of normal huma n urothelium. Explant cultures were established from ureters and expos ed to 5 ng/ml of the derivative. This level had been demonstrated prev iously to induce a variety of changes associated with initiation of ca rcinogenesis. Proliferation of the cultures was increased following ex posure to the carcinogen, and the gap junction intercellular communica tion was reversibly inhibited. Examination of the connexin 43 protein and message status showed that the mRNA was unaffected, but the protei n was not detectable using anti-connexin 43 antibody. The expression o f the protein recovered within 24 h of removal of the carcinogen, indi cating that the continued presence of the agent was necessary. Given t he roles of cell proliferation and cell communication in carcinogenesi s, the results may suggest a mechanism involving pre- or post-initiati on deregulation of cell communication systems. Whether the enhanced gr owth is a separate effect or a consequence of reduced communication is an intriguing question. Copyright (C) 1996 Elsevier Science Inc.