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Journal of Environmental Pathology, Toxicology and Oncology

Impact factor: 0.877

ISSN Print: 0731-8898
ISSN Online: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.2013006778
pages 29-39

Chronic Chlorpyrifos Exposure Does Not Promote Prostate Cancer in Prostate Specific PTEN Mutant Mice

Robert U. Svensson
Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242
Nadine L. Bannick
Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242
Maximo J. Marin
Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242
Larry W. Robertson
Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa
Charles F. Lynch
Department of Epidemiology, College of Public Health, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242
Michael D. Henry
Department of Pathology, Holden Comprehensive Cancer Center and Roy J. and Lucille A. Carver College of Medicine, Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242

ABSTRACT

Environmental factors are likely to interact with genetic determinants to influence prostate cancer progression. The Agricultural Health Study has identified an association between exposure to organophosphorous pesticides including chlorpyrifos, and increased prostate cancer risk in pesticide applicators with a first-degree family history of this disease. Exploration of this potential gene-environment interaction would benefit from the development of a suitable animal model. Utilizing a previously described mouse model that is genetically predisposed to prostate cancer through a prostate-specific heterozygous PTEN deletion, termed C57/Luc/Ptenp+/−, we used bioluminescence imaging and histopathological analyses to test whether chronic exposure to chlorpyrifos in a grain-based diet for 32 weeks was able to promote prostate cancer development. Chronic exposure to chlorpyrifos in the diet did not promote prostate cancer development in C57/Luc/Ptenp+/− mice despite achieving sufficient levels to inhibit acetylcholinesterase activity in plasma. We found no significant differences in numbers of murine prostatic intraepithelial neoplasia lesions or disease progression in chlorpyrifos versus control treated animals up to 32 weeks. The mechanistic basis of pesticide-induced prostate cancer may be complex and may involve other genetic variants, multiple genes, or nongenetic factors that might alter prostate cancer risk during pesticide exposure in agricultural workers.