Genetics of susceptibility to radiation-induced lymphomas, leukemias and lung tumors studied in recombinant congenic strains.

The genetic control of susceptibility to radiation-induced tumors in mice has been tested using the series of 20 CcS/Dem (CcS) Recombinant Congenic Strains, each carrying a different random set of 12.5% of genes of the resistant strain STS/A (STS) on the genetic background of the susceptible strain BALB/cHeA (BALB/c). Two classes of tumors were frequently observed: tumors of the haematopoietic system (lymphomas, myelocytic leukemias) and lung tumors. The results indicate that the genes controlling various aspects of tumor development were segregated in the CcS strain series. Large inter-strain differences were observed in the incidence of lung tumors. With lymphomas and leukemias, we not only observed strain differences in the incidence of tumors and in the latency of their development but also in the type of tumors (T- vs. B-cell lymphomas, myelocytic tumors) and in the frequency of their localized or disseminated (leukemic) form. Surprisingly, the myelocytic tumors, which occur very rarely or not at all in the parental strains BALB/c and STS or in their crosses, developed with high frequency in one of the CcS strains (CcS-2), indicating a unique combination of genes in this strain, which facilitates the development of myelocytic tumors. The effect of these genes is suppressed in the genetic composition of the parental strains. Tests of crosses of the resistant-strain CcS-13 with BALB/c indicated a suggestive linkage of a susceptibility gene for lymphomas to chromosome 5. These tests of the CcS strains illustrate the genetic complexity of the control of radiation-induced tumors in mice and suitability of these model systems to study their different facets. Copyright 1999 Wiley-Liss, Inc.