Expression of 44-kilodalton oncofetal antigen as a premalignancy marker in X irradiation-induced murine T-cell lymphoma.

Abstract

Oncofetal antigens (OFAs) are found on the surface of murine and human midgestation fetal cells, in human and rodent tumor tissues, and on human and rodent tumor and embryonic cell lines but not in normal neonatal or adult human and rodent tissue. The usefulness of OFA as an early indicator of lymphoma development was evaluated. With the use of monoclonal antibody directed against a 44-kd glycoprotein, cells from the thymus and spleen of RFM/UnCr mice receiving whole-body, split-dose x irradiation (1.75 Gy once a week for 4 weeks) or cells from these organs from control (nonirradiated) mice were analyzed for the presence of OFA in the flow cytometer and in limited intrathymic transplant. OFA was detected on thymocytes from 75% of irradiated mice by 2 months after treatment, reflecting eventual lymphoma development in the irradiated controls by flow cytometry and in intrathymic transplant. In general, the number of thymuses expressing OFA and the percentage of OFA+ cells increased with time after irradiation. By 4 months, OFA+ splenocytes were present, but only in mice possessing OFA+ thymocytes. Serially tested, irradiated RFM mice that never expressed OFA in the thymus reflected the percentage of irradiated RFM/UnCr mice that never developed lymphomas. This observation was also made in irradiated C57BL/6N mice, which attests to the tumor specificity of OFA expression. Spleen immunoglobulin-positive cells were decreased, while CD4+ and CD8+ cells were greatly increased. Indirect evidence of CD4/CD8 expression on OFA+ splenocytes suggests that the newly forming lymphomas were of immature T-cell origin. Major histocompatibility antigen expression did not vary significantly. Histopathologic examination revealed radiation-induced lymphomas in OFA-positive tissues characterized by a monomorphic population of large blastic immature lymphoid cells. The early expression of OFA in radiation-induced oncogenesis was established. OFA expression significantly preceded clear histologic evidence of malignant T cells or clinical lymphoma in irradiated RFM/UnCr mice that went on to develop T-cell lymphomas.