Effect of bcl-2 deficiency on the radiation response of clonogenic cells in small and large intestine, bone marrow and testis

Purpose: Overexpression of bcl-2 protects against radiation induced apoptos is in lymphohaematopoietic cell types in vivo, whilst bcl-2 deficiency radi osensitizes murine T-lymphocytes in vitro. However, there are few data rega rding the influence of bcl-2 deficiency on the radiosensitivity of non-lymp hoid cell types. The purpose of this study was to investigate the role of b cl-2 in the clonogenic radiation response of intestinal crypts, bone marrow progenitor cells and testicular stem cells. Method: Survival curves were obtained for each cell type from bcl-2 null (- /-), heterozygote (+/-) and wild type (+/+) mice. Crypt survival in the sma ll and large intestine was assessed using the crypt microcolony assay. Comm itted haemopoietic progenitors were assayed using in vitro colony-forming c ell (CFC) assays and survival of clonogenic spermatogonia was assessed by s coring regenerative tubules at 35 days post-irradiation. Results: There was no difference in small intestine crypt survival between the three genotypes. In the colon, there was a tendency towards lower clono gen survival in the +/- and +/+ animals. Haemopoietic in vitro CFC from -/- animals showed lower survival in comparison to +/+ mice, but spermatogonia l stem cells were comparatively more radioresistant. Conclusions : Deficiencies in bcl-2 affect the radiation response of differ ent cell populations in small but different ways. This may be due to variat ions between cells in their innate capacity for apoptosis, their dependence on different members of the bcl-2 family gene and their cell-cycle status and p53 expression.