Effect of bnu treatment on leukaemogenesis in lethally irradiated akr mice restored with bone-marrow and spleen cells

Abstract

The leukaemogenic effect of N‐butyl‐N‐nitrosourea (BNU) was studied in normal and thymectomized AKR mice which were lethally irradiated and restored with either bone‐marrow (BM) or spleen cells from (AKR × AKR/T1ALD)F₁ donors. In some instances T1ALD thymic cells were added to the restorative inoculum. It was possible to determine the origin of the leukemic cells by the metacentric marker chromosomes of T1ALD. The T‐ or B‐cell characteristics were further ascertained by the cytotoxicity test for θ antigen and the EAC rosette test. All leukaemias whether thymic (TLS) or extra‐thymic (ETL), developed from donor bone‐marrow or spleen cells and never from the injected thymic cells. In non‐thymectomized animals BNU increased the percentage of TLS and shortened their latency. Most of TLS which occurred after BNU treatment of BM‐restored mice were θ‐negative whereas the majority of TLS which occurred in controls and in spleen‐restored animals were θ‐positive. This suggests that during their maturation process BM‐derived T precursors transit through a θ‐negative compartment. This compartment does not reach a similar size during the maturation process of the spleen‐derived precursors. Adding thymic cells to the restorative inoculum enhanced leukaemogenesis and suppressed θ‐negative TLS in BM‐restored mice. Thymectomized mice, restored either by BM or spleen, had a low incidence of ETL which was not significantly increased by BNU treatment except in the case of mice restored with spleen cells. The leukaemic cells of one ETL were θ‐positive whereas all the other leukaemias had no detectable T or B marker. The percentage of ETL was higher in thymectomized mice treated with BNU alone than in those previously subjected to irradiation and restoration. These results strongly suggest that a θ‐negative T precursor could be involved in extra‐thymic leukaemogenesis but the possible involvement of a B precursor cannot be ruled out unless experiments are carried out with specific markers of T‐ and B‐cell sub‐classes.