Effect of testosterone on growth of P388 leukemia cell line in vivo and in vitro. Distribution of peripheral blood T lymphocytes and cell cycle progression.

In transplanted mice, the P388 tumor grew better in castrated than in non castrated (NC) mice. The proportion of CD8+ in the blood was more numerous in NC mice. The T cell subsets (CD4+ and CD8+) were also high in the mice with small tumor tissue (<10 mg). The correlation observed between the tumor weight and T cell subset in PBL and in the mice with small tumors could confirm the important intervention of CD4+ and CD8+ cells to inhibit growth of tumor. Depo-testosterone (DT) injection reduced strongly weight and tumor growth in mice and DT administration induced a significant increase in the percentage of blood CD8+ cells in grafted mice. The effect of DT was studied on the cell cycle progression, in the tumor tissue of P388 tumor bearing BDF1 mice and in the P388 murine leukemia cell line in culture. The cell cycle analysis showed that DT decreased both the cells in S phase and the proliferating leukemic cells, with accumulation of the cells in G0/G1 phase. The testosterone can inhibit the proliferation of leukemic cells with a pharmacological dose (10-7 M). This growth inhibition dose and time dependent was associated with cell cycle arrest; P388 cells accumulates in G0/G1 phase. We also observed a correlation between tumor weight and the percentage of cells in G0/G1 and the relative number of cells in proliferative state (S + G2/M). Our experiments showed that testosterone prevents the growth of tumor: indirectly by modulation of subsets T cells distribution and directly by alteration of the cell cycle.