title: Chronic chlorpyrifos exposure does not promote prostate cancer in prostate specific PTEN mutant mice.
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.
authors.affiliation: Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Robert U
authors.initials: RU
authors.lastname: Svensson
authors.forename: Nadine L
authors.initials: NL
authors.lastname: Bannick
authors.forename: Maximo J
authors.initials: MJ
authors.lastname: Marin
authors.forename: Larry W
authors.initials: LW
authors.lastname: Robertson
authors.forename: Charles F
authors.initials: CF
authors.lastname: Lynch
authors.forename: Michael D
authors.initials: MD
authors.lastname: Henry
mesh_terms: D000110:Acetylcholinesterase / Q000097:blood; D000284:Administration, Oral; D000818:Animals; D004390:Chlorpyrifos / Q000008:administration & dosage / Q000009:adverse effects*; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D017353:Gene Deletion; D059647:Gene-Environment Interaction; D007306:Insecticides / Q000008:administration & dosage / Q000009:adverse effects*; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors
chemical_list: D007306:Insecticides; D000110:Acetylcholinesterase; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D004390:Chlorpyrifos