This application seeks to continue the progress made in analysis of oncogenes activated in a well-defined experimental tumor model system. The novel oncogenes that were previously identified as being activated in rat nasal squamous carcinomas induced by inhalation of methylmethane sulfonate, dimethylcarbamyl chloride, and beta-propiolactone will be further characterized after molecular cloning of the genes. Alternative cloning strategies will include ligation or cotransfection of marker sequences such as genes for amber mutation suppression or antibiotic resistance. Once the novel nasal tumor oncogenes have been cloned, they will be characterized by DNA sequence analysis and their chromosomal location, levels of expression in various tissues and mechanism(s) of activation will be investigated. The importance of tissue as well as carcinogen specificity in oncogene activation, and the issue of oncogene activation as a function of neoplastic progression in an animal tumor model will be addressed. Chemical carcinogens known to induce malignant and benign tumors of several histologic types in the nasal cavity after exposure by inhalation will be used to generate panels of tumors. Activated oncogenes in these tumors will be identified by the NIH3T3 transfection or the cotransfection/nude mouse tumorigenesis assays, followed by Southern blot hybridization analysis. The hypothesis that certain oncogenes are actively involved in cellular transformation of particular tissue types and not others will be tested by transfecting purified oncogenes into cultures of epithelial cells. Increased understanding of the molecular mechanisms by which certain genes are activated in specific cell types during progression to malignancy and the relationship between carcinogenic etiology and such oncogene will contribute to knowledge of the nature of environmental carcinogenesis in animals and man, and will aid in the development of strategies for prevention, intervention or protection against cancer for exposed or susceptible populations.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA036342-06
Application #
3173893
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1984-08-01
Project End
1992-05-31
Budget Start
1989-06-13
Budget End
1990-05-31
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost
Name
New York University
Department
Type
Schools of Medicine
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012
Randall, T D; Parkhouse, R M; Corley, R B (1992) J chain synthesis and secretion of hexameric IgM is differentially regulated by lipopolysaccharide and interleukin 5. Proc Natl Acad Sci U S A 89:962-6
Cosma, G N; Wirgin, I I; Marchok, A C et al. (1990) Ha-ras oncogene mutations in cell lines derived from rat tracheal implants exposed in vivo to 7,12-dimethylbenz[a]anthracene. Mol Carcinog 3:258-63
Garte, S J; Burns, F J; Ashkenazi-Kimmel, T et al. (1989) An experimental model for oncogene activation during tumor progression in vivo. Anticancer Res 9:1439-46
Garte, S J; Hochwalt, A E (1989) Oncogene activation in experimental carcinogenesis: the role of carcinogen and tissue specificity. Environ Health Perspect 81:29-31
Cosma, G N; Marchok, A C; Garte, S J (1989) Oncogene expression in cell lines derived from rat tracheal implants exposed in vivo to 7,12-dimethylbenz[a]anthracene. Mol Carcinog 2:268-73
Hochwalt, A E; Wirgin, I; Felber, M et al. (1988) Detection of novel non-ras oncogenes in rat nasal squamous cell carcinomas. Mol Carcinog 1:4-6
Hochwalt, A E; Solomon, J J; Garte, S J (1988) Mechanism of H-ras oncogene activation in mouse squamous carcinoma induced by an alkylating agent. Cancer Res 48:556-8
Sawey, M J; Hood, A T; Burns, F J et al. (1987) Activation of c-myc and c-K-ras oncogenes in primary rat tumors induced by ionizing radiation. Mol Cell Biol 7:932-5
Garte, S J; Currie, D D; Troll, W (1987) Inhibition of H-ras oncogene transformation of NIH3T3 cells by protease inhibitors. Cancer Res 47:3159-62
Hood, A T; Currie, D; Garte, S J (1987) Establishment of a rat nasal epithelial tumor cell line. In Vitro Cell Dev Biol 23:274-8

Showing the most recent 10 out of 14 publications