Arsenic stimulates bladder epithelial cell proliferation.
Simeonova-PP; Matheson-JM; Flood-L; Luster-MI; Toriumi-W; Germolec-D
Toxicologist 1999 Mar; 48(1-S):281
Epidemiological studies have demonstrated a strong correlation between increased arsenic concentrations in drinking water and the incidence of bladder cancer in human. Additionally, it has been reported that dirnethylarsinic, one of the metabolites of inorganic arsenicals, promotes nitrosamine induced rat urinary bladder carcinogenesis. We have used in vivo and in vitro models to analyze the effect of inorganic arsenic (As3+) on bladder epithelial cells. Rats treated with arsenic in the drinking water (0.02%) had high levels in the urine of total arsenic represented by DMA, MMA and As3+, and demonstrated an increase in bladder epithelial cell proliferation in 4 weeks. The proliferative changes were documented by HE staining, PCNA immunostaining and electron microscopy. Consistent with the in vivo data, arsenic induced an increase in [3-H) thymidine incorporation in several bladder epithelial cell lines, a marker for DNA synthesis and cell proliferative response. Furthermore, arsenic stimulated the activation of transcription factors associated with modulation of the growth factor expression and control of the cell cycle of bladder epithelial cells, including AP-l. Taken together, these studies suggest that arsenic-induced bladder cancer may be associated with the ability of arsenic to directly stimulate bladder epithelial cell growth. Cell proliferation alone can provide an explanation of carcinogenesis. Arsenic can promote cell proliferation of previously initiated cells or the rapid cell proliferation can be prerequisite for increased mutational rate.
Toxins; Toxicology; Toxic-materials; Arsenic-poisoning; Arsenic-compounds; Bladder-cancer; Bladder-disease; Bladder-disorders; Cancer; Carcinogens; Laboratory-animals; Animal-studies; In-vivo-study; In-vitro-study
The Toxicologist. Society of Toxicology 38th Annual Meeting, March 14-18, 1999, New Orleans, Louisiana