Cytogenetic study of eight new cases of radiation-induced solid tumors

Radiation-induced tumors were selected according to the criteria defined by Cahan (1948) for sarcomas. Cell cultures and/or xenografts in nude mice we re performed with biopsies obtained from second primary rumors. Karyotypes of eight tumors were established after R-banding. After comparison with lit erature data on 15 other cases, two distinct cytogenetic patterns could be distinguished. One was characterized by polyclonal karyotypes, of which a l arge proportion were simple and carriers of balanced translocations. Anothe r one was characterized by monoclonal chromosome alterations observed in hi ghly aneuploid and complex karyotypes, in which many deletions were observe d. These two different patterns could be related to the modality of metapha se harvesting. Polyclonal karyotypes were preferentially observed after lon g-term cultures, and monoclonal karyotypes after short-term cultures or xen ografts. The following scheme of radiation oncogenesis is proposed: al indu ction of recessive gene mutations including that of tumor suppressor genes; b) accumulation of genomic alterations in the irradiated tissue with aging including deletions or mutations of normal alleles from mutated tumor supp ressor genes; and c) loss of tumor suppressor gene function and initiation of a multistage tumor development and progression. Polyclonal abnormalities are assumed to exist in noncancerous cells which acquired radiation-induce d chromosome aberrations. Published by Elsevier Science Inc.