Influence of serum thymic factor (FTS) on radiation-induced leukaemogenesis in thymectomized AKR mice

Abstract

The influence of serum thymic factor (FTS) on extrathymic leukaemogenesis induced in thymectomized AKR mice by fractionated sub-lethal irradiation was studied. Thirty-day-old thymectomized mice were submitted to four doses at weekly intervals (1.75 Gy) and thereafter treated with FTS (1 ng) for 9 days. Two groups were restored with either bone marrow or spleen cells prior to FTS treatment. In another group mice were treated with FTS (12 ng) for 1 month after thymectomy and prior to irradiation. Results indicated that primarily irradiation and FTS, and, to a lesser extent, restoration and age of the mice at the time of their first radiation exposure influenced leukaemogenesis. Irradiation increased the spontaneous low incidence of extrathymic leukaemia (5%) up to 50%. Although nothing is yet known about the expression of endogenous retroviruses in thymectomized AKR mice, the possible expression of leukaemogenic recombinants, either identical to or different from mink-cell-focus-inducing viruses (MCF), might explain this enhancing effect of radiation on leukaemogenesis. Mice developed two types of leukaemias: "null" leukaemias whose cells bore no detectable theta antigen or surface immunoglobulin, and B leukaemias. Among the null leukaemias, two kinds could be distinguished: "early" ones which were observed before 450 days, and in which BM and spleen were similarly involved, and "late" ones which displayed the same characteristics as B leukaemias, i.e. delayed appearance (after 450 days) and splenic origin. Although FTS did not modify the overall frequency of leukaemias, it increased significantly the incidence of the "early" null ones. It had no effect on the frequency or the latency of late null and B leukaemias. Any population of theta-negative T cells sensitive to FTS could be an acceptable candidate for "early" null leukaemogenesis. The origin of "late" null leukaemias remains an open question.