Pilot Project:2 B(a)P Induced Activation of Prostatic Specific Genes

Meharry Medical College, Nashville TN

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Abstract

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