A 60 kd oncofetal protein (OFP-60) earlier shown to be associated with all cancers regardless of site, but not with normal tissues, also appears to be specifically and consistently induced in adult target tissues by carcinogens. Preliminary studies suggest this induction occurs during the initiation phase. The long-term objective is to establish the significance of the association of OFP-60 with the carcinogenic process, since the consistent and specific association of a protein with carcinogenesis may not only provide insights into the mechanisms involved but may also open new approaches to cancer prevention and in particular cancer chemotherapy.
The specific aims i nclude (i) a study of the kinetics of induction by various carcinogenic regimens with particular attention to differential changes in the initiation and promotion phases; (ii) a quantitation of induction with reference to DNA damage, prenoplastic lesions and tumor incidence; (iii) an assessment of the occurrence of OFP-60 in preneoplastic lesions and to identify the cell type producing OFP-60 as a measure of its usefulness as a marker (iv) further studies demonstrating the specificity of this induction for carcinogens, (v) to study the relationship of the blood and tissue concentrations of OFP-60 and mechanisms underlying the half-life in blood and (vi) to establish the biochemical effects of this apparent regulatory protein. Measurements of OFP-60 will be made on both plasma and target tissues by biochemical, immunochemical and histochemical techniques. The study will focus on hepato-carcinogenesis in the rat. Although a polyclonal antibody to OFP-60 is now available, this is inadequate for most of the immunochemical studies planned, necessitating the production of monoclonal antibody to OFP-60.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
3R01CA042886-01S1
Application #
3184544
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1986-08-01
Project End
1990-01-31
Budget Start
1986-08-01
Budget End
1988-01-31
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Ohio State University
Department
Type
Schools of Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
Runge, S W; Larroya-Runge, S N; Schumm, D E et al. (1991) Development and use of monoclonal antibodies against an oncofetal protein associated with carcinogenesis and tumorigenesis. Immunol Invest 20:269-86
Stromberg, P C; Grants, I; Schumm, D E et al. (1991) Expression of an oncofetal protein (OFP) in rat and human leukemia cells. Leuk Res 15:427-33
Powis, G (1991) Signalling targets for anticancer drug development. Trends Pharmacol Sci 12:188-94
Runge, S W; Larroya, S; Schumm, D E et al. (1989) Developmental changes in expression of a tumor-associated protein in the rat fetus. J Cell Biochem 41:135-7
Schumm, D E; Tejwani, R; Webb, T E (1989) Hybridization analysis of RNA transported from rat liver nuclei in response to 35 kDa normal and 60 kDa messenger RNA transport factors. Biochim Biophys Acta 1009:54-60
Oredipe, O A; Schumm, D E; Mercurio, F et al. (1989) A carcinogenesis- and tumorigenesis-associated rat fetal protein: an immuno-histochemical and immuno-biochemical study utilizing a new monoclonal antibody, MOFP. Carcinogenesis 10:2175-81
Walaszek, Z; Hanausek-Walaszek, M; Webb, T E (1988) Repression by sustained-release beta-glucuronidase inhibitors of chemical carcinogen-mediated induction of a marker oncofetal protein in rodents. J Toxicol Environ Health 23:15-27