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Oncogenes and growth factors as indicators of carcinogen exposure
T Jussila1, M Mäkinen, F Stenbäck
1Department of Pathology, University of Oulu, Finland.
Abstract:
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.
Insights
Oncogene and growth factor expression increases during skin cancer development in mice, even in resistant strains. These changes are linked to carcinogen exposure but require further study for use as exposure indicators.
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- Skin carcinogenesis involves complex cell growth regulation pathways.
- Understanding alterations in these pathways is crucial for identifying carcinogen exposure indicators.
- Different mouse models (NMRI, DBA/2, SKH/1) exhibit varying responses to carcinogens.
Purpose of the Study:
- To investigate the expression of cell growth regulators during experimental skin carcinogenesis.
- To compare these expressions across different mouse strains and carcinogen types (UV, chemical).
- To assess the potential of these markers as indicators of carcinogen exposure.
Main Methods:
- Morphological and immunohistochemical analyses were employed.
- Expression levels of growth factors (TGF-α, EGF), receptors (EGFR/c-erbB-1, c-erbB-2/neu), c-myc, Harvey-Ras, and p53 were studied.
- Tumor formation was induced by UV irradiation and chemical carcinogens in various mouse models.
Main Results:
- Increased expression of oncogenes and growth factors was observed in skin during tumor development, starting in pre-malignant stages.
- Elevated expression persisted even in carcinogen-resistant DBA/2 mice.
- Specific initiated cells were not identifiable prior to morphological changes.
Conclusions:
- Oncogene and growth factor expression are associated with carcinogenic effects, offering insights into mechanisms of action.
- The utility of these markers for analyzing hazardous agent exposure requires further investigation.