? In the United States there are about 30,000 new oral cancer cases per year. Oral cancer is often associated with tobacco product use but current prevention methods to reduce numbers of new cases are ineffective. An oral cancer model paralleling human exposure to tobacco carcinogens is expected to enhance our ability to prevent oral cancer. Exisiting oral cancer models have generally relied upon synthetic carcinogens minimizing parallels to human exposure experience and changes in oral mucosa. Other environmental agents, tobacco specific N-nitrosamines, or arecoline derived from the betal nut either lack the ability to initiate oral carcinogenesis or have not been evaluated extensively for cell biology mechanisms. Few oral carcinogenesis studies have examined the cellular events in the oral keratincyte following exposure to tobacco carcinogen. Our goal is to establish a tobacco carcinogen induced oral carcinogenesis model, which can be replicated by others for prevention of oral cancer. This model will have a high tumor incidence and multiplicity after a relatively short period of induction. Tumor induction in tongue and floor of the mouth will parallel sites in humans. This model will also be extendable to other models such as the guinea pig and knock-out mouse to study prevention. Environmental and tobacco carcinogens, fjord structured, dibenzo[a,I]pyrene, diB[a,I]P will be compared to a bay region chemical, benzo[a]pyrene, B[a]P, an established oral carcinogen in the hamster. In a preliminary study, diB[a,I]P was observed to be a more potent carcinogen than B[a]P. This result requires confirmation which we will obtain from the following studies:
Aim la. A dose response effect for diB[a,I]P/B[a]P assessing tumor incidence and multiplicity. lb. Detection of DNA adduct type and presence in histologic sites and p53 mutations during oral carcinogenesis. lc. Assessments of membrane (aryl hydrolase) and cytoplasmic phase I and II enzymes. ld. Confirmation of early cellular initiation and promotion events critical to our understanding for prevention of oral cancer. ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
1R03CA109940-01
Application #
6830343
Study Section
Special Emphasis Panel (ZCA1-SRRB-Q (M1))
Program Officer
Steele, Vernon E
Project Start
2004-09-20
Project End
2006-08-31
Budget Start
2004-09-20
Budget End
2005-08-31
Support Year
1
Fiscal Year
2004
Total Cost
$77,500
Indirect Cost
Name
University of Illinois at Chicago
Department
Dentistry
Type
Schools of Dentistry
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612