Arsenic-induced mitogenic cell signaling pathways.
Proceedings of the 28th Annual Conference and Special Symposium on Arsenic Contamination in Ground Water and its Health Effects, February 14-16, 2003. Jadavpur, India: Indian Institute of Chemical Biology, 2003 Feb; :6
Environmental or occupational exposure to arsenic is associated with a greatly increased risk of skin, urinary bladder and respiratory tract cancers in arseniasis-endemic areas throughout the world. We have employed in vitro and in vivo models to examine the effects of arsenic on the urinary bladder epithelium. Mice exposed to 0.01 percent sodium arsenite in the drinking water demonstrated marked hyperproliferation of the bladder uroepithelium within 4 weeks after initiating treatment. The response was accompanied with accumulation of arsenic and induction of activating protein-1 (AP-1) in the urinary bladder tissue. Furthermore, arsenic induced activation of major mitogenic mediators, such as epidermal growth factor receptor (EGFR) and extracellular signal-regulated protein kinase (ERK), in the uropeithelium. This response is also accompanied with increased levels of non-receptor tyrosine kinase c-Src interacting with the EGFR. Consistent with these in vivo observations, arsenic activates c-Src in a human uroepithelial cell line. Using pharmacological and genetic inhibition of Src, we found that c-Src activity is a prerequisite for EGFR and ERK activation in these cells. In conclusion, arsenic shares many properties of tumor promoters by affecting specific cell signal transduction pathways responsible for cell proliferation of initiated cells or increasing the mutational rate.
Environmental-exposure; Environmental-hazards; Environmental-health; Occupational-exposure; Occupational-hazards; Occupational-health; Skin-cancer; Skin-disorders; Urogenital-system; Urogenital-system-disorders; Bladder-cancer; Bladder-disorders; Respiratory-system-disorders; In-vitro-study; In-vivo-study; Arsenates; Arsenic-poisoning; Cell-alteration; Cell-damage; Cell-morphology; Heavy-metals; Heavy-metal-poisoning
Abstract; Conference/Symposia Proceedings
Proceedings of the 28th Annual Conference and Special Symposium on Arsenic Contamination in Ground Water and its Health Effects, February 14-16, 2003