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.
