INHIBITORY EFFECTS OF SIZOFIRAN ON ANTICANCER AGENT-INDUCED OR X-RAY-INDUCED SISTER-CHROMATID EXCHANGES AND MITOTIC BLOCK IN MURINE BONE-MARROW CELLS

The inhibitory effects of a biological response modifier (BRM), sizofi ran, on sister chromatid exchanges (SCEs) in the bone marrow cells of mice treated with various anticancer agents or irradiation were invest igated. Sizofiran (10 mg/kg i.m.) inhibited SCEs induced by mitomycin C (2 mg/kg i.v.), adriamycin (20 mg/kg i.v.) and cyclophosphamide (20 mg/kg i.v.) by about 20%, respectively. Analysis of the SCEs in vivo a fter irradiation plus sizofiran indicated that SCE levels were signifi cantly lower than those observed in mice exposed to irradiation withou t sizofiran. Moreover, the effects of sizofiran were dependent on the timing of administration. Our results indicated that sizofiran should be administered simultaneously or soon after irradiation in order to m inimize damage. Sizofiran also markedly restored the bone marrow cell mitosis which had been suppressed by anticancer agents, and this actio n was closely correlated with the prevention of increase in SCEs. Thes e results indicate that in addition to immunopotentiating activity, si zofiran may play a role in preventing chromosomal damage induced by ca ncer chemotherapy and radiotherapy.