Das Projekt "Knochensarkome und Tumoren des haematopoetischen Systems durch niedrig dosierte Bestrahlung" wird vom Umweltbundesamt gefördert und von GSF-Forschungszentrum für Umwelt und Gesundheit, GmbH durchgeführt. General Information: The human radium A induced tumours, resulting from former industrial occupation as dial painters with 226Ra and medical treatment with 224Ra, continue to provide basic information on the effects of internal irradiation and radio carcinogenesis in man. Animal experimentation and in vitro systems help to elucidate the problems of radiation hazards, and in addition increase our understanding of the mechanisms of radiation carcinogenesis. Bone tumours and tumours of the haematopoietic system have been induced experimentally by internal administration of many bone seeking radioactive isotopes. For several short lived radio nuclides we have the basic knowledge of dose dependence and protraction effects in radiation induced osteosarcomogenesis and leukaemogenesis. The additional induction of leukaemia, particularly at lower dose levels, raises the question of the target cell in alpha radiation oncogenesis. This is a further indication of the importance of extending studies of early events in haematopoietic and stroma bone marrow cells and osteogenic cells. Data from the epidemiological study on 224Ra patients also indicate the need for systematic investigations of the leukaemia risk after the incorporation of bone seeking radio nuclides. In addition experimental studies using 224Ra offer the possibility of estimating the plutonium risk in humans. In studies of different age periods the role of possible sensitive periods during the whole lifespan should be explored. In this proposal considerable emphasis is placed on molecular biological approaches to radiation carcinogenesis, both in appropriate animal models, in vitro systems and human tumours. Studies with oncogenic retroviruses have revealed new aspects of the molecular basis of carcinogenesis. Several groups of genes have been detected which are involved in the development of tumours. These genes are normal constituents of the genetic makeup of the cell, but in carcinogenesis they seem to be over expressed, mutated or combined with other genes. A more detailed molecular analysis of target genes for radiation carcinogenesis is envisaged. The research projects in this proposal are concerned with the general problem of radiation risk, especially with respect to radiation induced cancer. The quantitative analysis of dose effect relationships with special emphasis on time and quality factors, and the development and analysis of appropriate animal experiments and in vitro systems with the possibility of studying mechanisms of oncogenesis, will have immediate implications for improving the establishment of dose limits. Inclusion of the whole lifespan in the study of risk takes the age pattern of a real population into account. The determination of the genes and gene products responsible for radiation carcinogenesis would offer the possibility of defining the critical radiation doses which induce or activate events in the cellular genome subsequently leading to cell transformation. ...