Radiostrontium-Induced Oncogenesis and the Role of Immunosuppression I. Influence of 90Sr dose, adult thymectomy and antilymphocyteglobulin treatment on the development of neoplastic and preneoplastic lesions in the skeleton of CBA mice

Abstract

Ionizing irradiation by incorporated strontium-90 exerts two major effects: it induces tumours (mainly osteosarcomas and lymphoreticular tumours) and depresses the immune system. The interrelation between these functions, i.e. the significance of decreased immunological responsiveness in the oncogenic process, remains unclear. The influence of the ⁹⁰Sr dose and the role of immune modulation on the tumour yield, were investigated in young adult CBA mice. The animals were exposed to different single doses of ⁹⁰Sr and, in addition, some groups were subjected to long-term unspecific immune suppression by adult thymectomy (ATx) and/or prolonged antilymphocyteglobulin (ALG) treatment. The present paper (part I) reports on the effects of the treatments on bone tumour responses as reflected by incidence, multiplicity, latency time, histologic characteristics and growth behaviour. The histogenesis of osteosarcomas, as evidenced morphologically by preneoplastic and early neoplastic growth, is illustrated and discussed. The results demonstrate a positive dose-response relationship for osteosarcomas, in which the relative incidences of the various osteosarcoma subtypes were differentially affected. Thus, well-differentiated tumours were gradually replaced by less differentiated types as the dose decreased. A correlation was also observed between the incidence of osteosarcomas and that of assumed preneoplastic lesions in the same bones and sites. Immune suppression by ATx and/or ALG did not distinctly alter the neoplastic or preneoplastic responses at any dose-level of ⁹⁰Sr.