Background: These works were designed to investigate the influence of androgens (by castration and testosterone treatment) on growth and development of murine leukaemia cell line P388 in vitro and in vivo. To approach the mechanism of this hormone, the cell cycle was analysed in bone marrow cells and tumour tissue in vitro and on murine leukaemia cell line (P388) in culture. The anti-androgen CA was used to provide additional information concerning the androgen receptor in leukaemia cells.
Materials and methods: The effect of Depo-Testosterone (DT) and Cyproterone-Acetate (CA) were studied on growth tumour and cell cycle progression, in bone marrow and tumour tissue of intact or castrated P388 tumour-bearing BDF1 mice. In parallel the effect of various concentrations of DT (10-8, 10-7, 10-6, 10-4 M) was investigated on the proliferation and cell cycle of P388 leukaemia cell line in vitro.
Results: In P388 tumour-bearing mice, DT (0.5mg/100g body weight) treatment reduced strongly the weight and the appearance rate of tumour in non-castrated (NC) and castrated animals. In NC animals, the cell cycle analysis showed a significant decrease in the number of cells in S phase in tumour tissue under DT or CA treatment. Same results were obtained in bone marrow with DT only. The cells accumulate into G2/M and G0/G1 phases respectively. In vitro testosterone can inhibit the proliferation of leukaemic cells with a pharmacological dose of 10-7M. This growth inhibition was associated with cell cycle arrest in G0/G1 phase. This effect was dose and time dependent.
Conclusion: The data demonstrated that both in vivo and in vitro, testosterone prevent the growth of P388 leukaemia cells and induce changes in their cell cycle. The similar effect of CA and DT on tumour growth inhibition, in cell cycle of bone marrow and tumour tissue may suggest differences between androgen receptors of sexual organs and leukemic cells.