The long-range objective of the proposed research is to identify and analyze in sequential fashion, the key cellular and molecular events occurring and during oral carcinogenesis. Viable cell dissociates, full thickness whole mounts, and cryostatprepared microscope sections, of carcinogen-treated hamster buccal pouch epithelium (HBPE) will be examined for functional, histochemical, immunohistochemical, and morphological evidence of cells which have undergone one or more steps in the carcinogenic Process.
The specific aims are: 1) to (a) further characterize a unique keratinocyte population identified in cultures of carcinogen- initiated HBPE, and (b) evaluate its neoplastic potential using assays for production of transforming growth factors, in vitro growth characteristics, angiogenesis, and tumor formation following reimplantation into the autologous host, 2) to detect presumptive precancerous lesions in carcinogen-initiated HBPE using monoclonal antibodies against specific oncogene products, and 3) to determine whether extractable constituents of smokeless tobacco exert a promoting action on HBPE with an accompanying selection of focal cell populations rich in gamma-glutamyl transpeptidase activity. This research is based on the premise that a detailed analysis of oral carcinogenesis, which focuses on the relevant participating cell populations, will contribute to improved strategies for early detection of precancerous oral lesions and prevention of oral cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA034160-07
Application #
3171937
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1982-07-01
Project End
1990-11-30
Budget Start
1989-12-01
Budget End
1990-11-30
Support Year
7
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
Schools of Dentistry
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Nagabhushan, M; Line, D; Polverini, P J et al. (1992) Anticarcinogenic action of diallyl sulfide in hamster buccal pouch and forestomach. Cancer Lett 66:207-16
Hussong, J W; Polverini, P J; Solt, D B (1991) Resistant keratinocytes in 7,12-dimethylbenz[a]anthracene-initiated hamster buccal pouch epithelium. Carcinogenesis 12:617-22
Husain, Z; Fei, Y B; Roy, S et al. (1989) Sequential expression and cooperative interaction of c-Ha-ras and c-erbB genes in in vivo chemical carcinogenesis. Proc Natl Acad Sci U S A 86:1264-8
Solt, D B; Polverini, P J; Ray, S et al. (1988) Early neoplastic commitment of hamster buccal pouch epithelium exposed biweekly to 7,12-dimethylbenz[a]anthracene. Carcinogenesis 9:2173-7
Polverini, P J; Solt, D B (1988) Expression of the angiogenic phenotype by a subpopulation of keratinocytes derived from 7,12-dimethylbenz[a]anthracene-initiated hamster buccal pouch epithelium. Carcinogenesis 9:117-22
Solt, D B; Polverini, P J; Calderon, L (1987) Carcinogenic response of hamster buccal pouch epithelium to 4 polycyclic aromatic hydrocarbons. J Oral Pathol 16:294-302
Polverini, P J; Solt, D B (1986) Effect of in vivo carcinogen exposure on colony formation and growth of hamster buccal pouch keratinocytes in culture. Lab Invest 54:432-41
Cheifetz, S; Like, B; Massague, J (1986) Cellular distribution of type I and type II receptors for transforming growth factor-beta. J Biol Chem 261:9972-8
Solt, D B; Calderon-Solt, L; Odajima, T (1985) Rapid induction of carcinomas and gamma-glutamyl transpeptidase-rich clones in N-methyl-N-benzylnitrosamine-treated hamster buccal pouch. J Natl Cancer Inst 74:437-45
Calderon-Solt, L; Solt, D B (1985) Gamma-glutamyl transpeptidase in precancerous lesions and carcinomas of oral, pharyngeal, and laryngeal mucosa. Cancer 56:138-43