Benzo(a)pyrene [B(a)P] is a lipophilic aromatic hydrocarbon that belongs to the polycyclic aromatic? hydrocarbon family and has been implicated in toxicity and in increased incidence of cancer in various? organs. The incidence of advanced prostate cancer and mortality has been disproportionately high in some? population groups which have also been exposed to higher concentrations of aromatic hydrocarbons? (AHCs), the prototype of which is B(a)P. To test whether B(a)P alters the rate or extent of cancer? development, we propose to study a genetically engineered mouse model that permits the study of prostate? carcinogenesis in an experimentally amenable time frame. This unique LPB-Tag transgenic mouse model of? prostate cancer which develops a spatial pathological pattern of preneoplastic lesions and small foci of? bcally invasive carcinoma. The central hypothesis to be tested is that exposure to B(a)P aerosol at levels? experienced by human beings in certain environments results in alteration of prostatic function leading to? induction or acceleration of prostate cancer formation. This hypothesis can be narrowed down to two? questions. 1) Does B(a)P alter specific steroidal hormone and androgen events in a temporal manner to alter? prostatic function? and 2) Does B(a)P accelerate prostatic intraepithelial neoplasm (PIN) that progresses to? prostate adenocarcinoma?? We intend to address these questions and test our hypothesis that B(a)P accelerates prostate cancer? progression using two specific Aims.
Specific Aim I will exploit a range-finding study to determine the? disposition of B(a)P in the prostate of our mouse model in order to establish the dose of aerosolized B(a)P to? use in our subsequent studies.
Specific Aim II will determine the effect of B(a)P on the progression of? prostatic intraepithelial neoplasia (PIN) to adenocarcinoma monitoring both histopathological changes and? specific gene expression. In adddition, we will also assess relative proliferation rate of prostate tissues in? control and B(a)P exposed mice.? These studies will advance our knowledge of the role of environmental toxicants on the initiation and? progression of prostate cancer and provide preliminary data to seek extramural funding to delinate the? mechanism by which environmental pollutants, like the ubiquitous AHCs, alter initiation and progression of? cancer as a first step in the prevention, diagnosis, prognosis and better management of prostate cancer.? This will also help in redressing health disparity among our different population groups.
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