A NEW IMMUNOBIOLOGICAL VIEW OF RADIATION-PROMOTED LYMPHOMAGENESIS

Whole-body irradiation produces T-cell leukaemias/lymphomas (TCL) in s ome strains of inbred mice in an X-ray dose-related manner. Radiation biologists have related the rapid 'initiation' and early appearance of preleukaemic cells in these mice to unrepaired DNA damage inflicted b y radiation. Following initiation, radiation-altered thymic differenti ation fosters multi-step transformation changes in proto-oncogenes and suppressor gene expression in individual clones of non-invasive prele ukaemia cells as they progress to malignancy. The malignant clones ari sing from small numbers of initiated preleukaemia thymocytes become fu lly transformed only after several more months to a year after irradia tion in those strains of mice which develop T-cell lymphomas. When the RFM mouse was subjected to sublethal whole-body X-ray, only 50% of th e mice developed TCL by 6 months, yet nearly all developed preleukaemi a thymocytes. The T-cell-mediated immune response of the irradiated ho st has never been substantiated to contribute to malignant TCL develop ment. Until recently, X-ray-induced TCL were not known to carry common tumour rejection antigens TATA. However, several studies have reveale d that both preleukaemia cells and fully malignant TCL express an immu nogenic, common oncofoetal glycoprotein, termed 44 kD OFA. OFA-activat ed memory CD4 TH1 and CDS TCTL T-effector cells in irradiated mice exp ressing OFA. As most irradiated RFM mice exhibit preleukaemia thymocyt es yet only half develop rumours, this finding implicates active host T-cell effector responses in X-ray-initiated tumorigenesis. Further, t he recent discovery of OFA-specific CD8 Ts clones in irradiated mice, which inhibited cytotoxicity of CD8 clones to OFA or TSTA, may explain which mice develop T-cell lymphomas.