A new immunobiological view of radiation-promoted lymphomagenesis.
Whole-body irradiation produces T-cell leukaemias/ lymphomas (TCL) in some 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 by radiation. Following initiation, radiation-altered thymic differentiation fosters multi-step transformation changes in proto-oncogenes and suppressor gene expression in individual clones of non-invasive preleukaemia cells as they progress to malignancy. The malignant clones arising from small numbers of initiated preleukaemia thymocytes become fully transformed only after several more months to a year after irradiation 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 the mice developed TCL by 6 months, yet nearly all developed preleukaemia thymocytes. The T-cell-mediated immune response of the irradiated host has never been substantiated to contribute to malignant TCL development. Until recently, X-ray-induced TCL were not known to carry common tumour rejection antigens TATA. However, several studies have revealed that both preleukaemia cells and fully malignant TCL express an immunogenic, common oncofoetal glycoprotein, termed 44kD OFA. OFA-activated memory CD4 Tm and CD8 Ten. T-effector cells in irradiated mice expressing OFA. As most irradiated RFM mice exhibit preleukaemia thymocytes yet only half develop tumours, this finding implicates active host T-cell effector responses in X-ray-initiated tumorigenesis. Further, the 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.
Coggin
J H
JH
University of South Alabama, College of Medicine, Department of Microbiology and Immunology, Mobile 36688, USA.
Rohrer
J W
JW
Barsoum
A L
AL
D000818:Animals; D018960:Hyaluronan Receptors / Q000032:analysis / Q000235:genetics; D009052:Leukemia Virus, Murine / Q000235:genetics; D007953:Leukemia, Radiation-Induced / Q000235:genetics / Q000276:immunology / Q000821:virology; D015458:Leukemia, T-Cell / Q000235:genetics / Q000276:immunology* / Q000821:virology; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000276:immunology* / Q000821:virology; D051379:Mice; D009381:Neoplasms, Radiation-Induced / Q000235:genetics / Q000276:immunology* / Q000821:virology; D011289:Preleukemia / Q000209:etiology / Q000235:genetics; D011829:Radiation Dosage; D012190:Retroviridae / Q000235:genetics; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology; D016385:TATA Box; D013945:Thymoma / Q000209:etiology; D014916:Whole-Body Irradiation
D018960:Hyaluronan Receptors