Oncogenes and growth factors as indicators of carcinogen exposure.
The occurrence of different components of the cell growth regulation pathway as expressed in experimental skin carcinogenesis in haired carcinogen-sensitive NMRI, in haired carcinogen resistant DBA/2 mice and in hairless SKH/1 mice was studied by morphological and immunohistochemical methods. The results were compared with respect to neoplastic response, number of tumors, tumor behaviour and to the inducing agent (UV irradiation or chemical carcinogen), in order to increase our understanding of specific alterations in neoplastic development caused by extraneous agents and to determine their possible usefulness as indicators of carcinogen exposure. The expression of growth factors (transforming growth factor alpha and epidermal growth factor), growth factor receptors (epidermal growth factor receptor/c-erbB-1 and c-erbB-2/neu), cell signalling component c-myc, the nuclear transcription factor Harvey-Ras and the tumor suppressor gene p53, were studied in carcinogen- and UV-induced tumor formation in mouse. The results showed increased oncogene expression as well as growth factor expression in the skin during tumor development appearing early in neoplastic and premalignant conditions and becoming more distinct during neoplastic progression. Efforts to delineate specifically initiated cells prior to the appearance of morphologically detectable alterations including dysplasia, papilloma formation and squamous cell carcinomas, were unsuccessful. Increased staining by antibodies to growth factors and oncogenes were also observed in DBA/2 animals resistant to tumor formation. It is concluded that oncogene expression and growth factor protein deposits are associated with carcinogenic effects, partly explaining the mechanism of action of these agents, but the applicability, as such, for the analysis of potential hazardous agents needs further studies.
Jussila
T
T
Department of Pathology, University of Oulu, Finland.
Mäkinen
M
M
Stenbäck
F
F
D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D002273:Carcinogens / Q000633:toxicity*; D005260:Female; D006133:Growth Substances / Q000032:analysis*; D051379:Mice; D008811:Mice, Inbred DBA; D009857:Oncogenes / Q000187:drug effects*; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000737:chemistry* / Q000473:pathology
D014408:Biomarkers, Tumor; D002273:Carcinogens; D006133:Growth Substances