ONCOGENES AND GROWTH-FACTORS AS INDICATORS OF CARCINOGEN EXPOSURE

The occurrence of different components of the cell growth regulation p athway as expressed in experimental skin carcinogenesis in haired carc inogen-sensitive NMRI, in haired carcinogen resistant DBA/2 mice and i n hairless SKH/1 mice was studied by morphological and immunohistochem ical methods. The results were compared with respect to neoplastic res ponse, number of tumors, tumor behaviour and to the inducing agent (UV irradiation or chemical carcinogen), in order to increase our underst anding of specific alterations in neoplastic development caused by ext raneous agents and to determine their possible usefullness as indicato rs of carcinogen exposure. The expression of growth factors (transform ing growth factor alpha and epidermal growth factor), growth factor re ceptors (epidermal growth factor receptor/c-erbB-1 and c-erbB-2/neu), cell signalling component c-myc, the nuclear transcription factor Harv ey-Ras and the tumor suppressor gene p53, were studied in carcinogen- and W-induced tumor formation in mouse. The results showed increased o ncogene expression as well as growth factor expression in the skin dur ing tumor development appearing early in neoplastic and premalignant c onditions and becoming more distinct during neoplastic progression. Ef forts to delineate specifically initiated cells prior to the appearanc e of morphologically detectable alterations including dysplasia, papil loma formation and squamous cell carcinomas, were unsuccessfull. Incre ased staining by antibodies to growth factors and oncogenes were also observed in DBA/2 animals resistent to tumor formation. It is conclude d that oncogene expression and growth factor protein deposits are asso ciated with carcinogenic effects, partly explaining the mechanism of a ction of these agents, but the applicability, as such, for the analysi s of potential hazardous agents needs further studies.