Ovarian cancer is one of the leading causes of mortality due to cancer in women. There has been an increasing focus on developing new models for study of these cancers. Recently, gonadal tumors have been described in softshell clams (Mya arenaria) from Maine and hardshell clams (Mercenaria spp.) from Indian River, Florida. Prevalence of these histogenically similar tumors are as high as 40% in Maine and 60% in certain populations in Florida. Tumor incidence is correlated with the use of the phenoxyaretic arid herbicides 2,4-D and 2,4,5-T. While these chemicals are of relatively low toxicity, a by-product of their synthesis which is a common contaminant, 2,3,7,8,-tetra chlorodibenzo-p-dioxin, is a highly toxic compound. Recent studies of testicular cancer in dogs exposed to the same class of herbicides also implicated their role in the etiology of gonadal tumors. Epidemiology of human populations in the United States revealed that a significantly higher than average mortality due to cancer of the reproductive system in populations occupying the same areas as the tumor-bearing clams. These observations strongly suggest that environmental exposure to herbicides may contribute to the etiology of these cancers. We propose to explore this hypothesis by examining the molecular mechanisms of tumorigenesis in clams from the affected populations and in clams exposed to dioxin-containing sediments in the laboratory. We will focus on the roles of oncogenes and tumor suppressor genes in these tumors as well as the role of the Ah receptor.
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