Radioreductive effect of bestatin (Ubenimex) in BALB/c mice

The radioreductive effect of Bestatin (Ubenimex), a biological response modifier, was examined in BALB/c mice. Consecutive daily administrations from day 0 to day 3 after lethal irradiation resulted in a dose reduction factor (DRF) of 1.03. In haematological studies Bestatin enhanced the recovery of peripheral leucocytes in sublethally irradiated mice by activating colony-stimulating factors (CSF) in serum, leading to enhanced recovery of GM-CFC. There was no enhancement of CSF in BALB/c nude mice. On the other hand, Bestatin showed no effect on day 12 CFU-S and day 7 CFU-S after the sublethal irradiation, though there was a trend that the drug stimulated numbers of day 7 CFU-S after irradiation. These results strongly suggest that Bestatin enhanced the CSF activity by modulating T cell function, resulting in the augmentation of peripheral leucocytes and prolongation of survival of irradiated mice. This drug now used in the clinic proved to be modestly effective.