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.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Project (R01)
Project #
5R01RR008774-03
Application #
2284048
Study Section
Special Emphasis Panel (SSS (M3))
Project Start
1993-12-16
Project End
1996-07-31
Budget Start
1994-08-01
Budget End
1995-07-31
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Maine
Department
Zoology
Type
Schools of Arts and Sciences
DUNS #
City
Orono
State
ME
Country
United States
Zip Code
04473
Holbrook, Lauren A C; Butler, Rondi A; Cashon, Robert E et al. (2009) Soft-shell clam (Mya arenaria) p53: a structural and functional comparison to human p53. Gene 433:81-7
Butler, Rondi A; Kelley, Melissa L; Olberding, Kristen E et al. (2004) Aryl hydrocarbon receptor (AhR)-independent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on softshell clam (Mya arenaria) reproductive tissue. Comp Biochem Physiol C Toxicol Pharmacol 138:375-81
Olberding, Kristen E; Kelley, Melissa L; Butler, Rondi A et al. (2004) A HECT E3 ubiquitin-protein ligase with sequence similarity to E6AP does not target p53 for degradation in the softshell clam (Mya arenaria). Mutat Res 552:61-71
Butler, R A; Kelley, M L; Powell, W H et al. (2001) An aryl hydrocarbon receptor (AHR) homologue from the soft-shell clam, Mya arenaria: evidence that invertebrate AHR homologues lack 2,3,7,8-tetrachlorodibenzo-p-dioxin and beta-naphthoflavone binding. Gene 278:223-34
Brown, D J; Clark, G C; Van Beneden, R J (1998) A new cytochrome P450 (CYP30) family identified in the clam, Mercenaria mercenaria. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 121:351-60
Caporale, D A; Beal, B F; Roxby, R et al. (1997) Population structure of Mya arenaria along the New England coastline. Mol Mar Biol Biotechnol 6:33-9
Rhodes, L D; Van Beneden, R J (1997) Isolation of the cDNA and characterization of mRNA expression of ribosomal protein S19 from the soft-shell clam, Mya arenaria. Gene 197:295-304
Van Beneden, R J; Walker, C W; Laughner, E S (1997) Characterization of gene expression of a p53 homologue in the soft-shell clam (Mya arenaria). Mol Mar Biol Biotechnol 6:116-22
Van Beneden, R J (1997) Environmental effects and aquatic organisms: investigations of molecular mechanisms of carcinogenesis. Environ Health Perspect 105 Suppl 3:669-74
Brown, D J; Van Beneden, R J; Clark, G C (1995) Identification of two binding proteins for halogenated aromatic hydrocarbons in the hard-shell clam, Mercenaria mercenaria. Arch Biochem Biophys 319:217-24

Showing the most recent 10 out of 11 publications