Different cellular basis for the resistance of C3H and STS strain mice to the development of thymic lymphomas following fractionated whole-body irradiation: analysis using radiation bone marrow chimeras

Abstract

Purpose: B10 strain mice are susceptible to the induction of thymic lymphomas by fractionated whole-body X-irradiation (FI), whereas C3H and STS mice are resistant. The nature of the factors responsible for the strain difference in the susceptibility to thymic lymphomagenesis was investigated by using radiation bone marrow chimeras.

Methods: Radiation bone marrow chimeras were constructed in the reciprocal donor-host combinations of susceptible and resistant mice with use of Thy 1 markers that allow the genetic origins of thymocytes and thymic lymphomas to be determined.

Results: B10.Thy 1.1-->C3H, B10.Thy 1.1-->STS as well as B10.Thy 1.1-->B10 bone marrow chimeras manifested a high incidence of thymic lymphomas after FI-treatment, whereas C3H.Thy 1.1-->B10 and STS-->B10.Thy 1.1 as well as C3H.Thy 1.1-->C3H and STS-->STS chimeras manifested a low incidence of thymic lymphoma. Furthermore, FI-treatment of (B10.Thy 1.1+C3H)-->B10.Thy 1.1 mixed chimeras resulted in the generation of similar numbers of thymic lymphomas of B10 and C3H origins, whereas FI-treatment of (B10.Thy 1.1+STS)--> B10.Thy 1.1 mixed chimeras preferentially induced thymic lymphomas of B10 origin.

Conclusions: (1) genetic factors responsible for the strain-dependent susceptibility and/or resistance to FI-induced lymphomagenesis exert their effects entirely on bone-marrow derived cells, (2) host environments of C3H and STS resistant mice are not inhibitory for the development of thymic lymphomas and (3) the resistance of STS mice to FI-induced thymic lymphomagenesis is an intrinsic property of thymocytes, whereas C3H and B10 thymocytes themselves are similarly susceptible for FI-induced thymic lymphomagenesis.