Date of Graduation
Davis College of Agriculture, Natural Resources and Design
CYP1A1 metabolizes polycyclic aromatic hydrocarbons (PAHs), such as those in cigarettes, to reactive intermediates which interact with DNA and lead to cancer. Silica is a lung carcinogen. Epidemiology studies of silica and lung cancer are not all positive. A possible explanation for these inconsistencies may be that silica is a modifier of PAH metabolism and, thus, cigarette smoke carcinogenesis. We hypothesize that crystalline silica exposure alters CYP1A1 expression, thereby modifying lung cancer risk. Rats exposed to both crystalline silica and the model PAH, beta-naphthoflavone (NF), a CYP1A1 inducer have significantly decreased CYP1A1 enzymatic activity and CYP1A1 protein expression. In the proximal alveolar region of NF-exposed rats, silica exposure increases markers of alveolar type II cells but decreases proportional CYP1A1 expression in type II cells as detected by immunofluorescence. Our experiments support the hypothesis that silica is a negative modifier of CYP1A1 induction by PAH.
Battelli, Lori A., "Exposures to silica and inducers of xenobiotic metabolism in the rat lung" (2004). Graduate Theses, Dissertations, and Problem Reports. 2063.