RADIOPROTECTIVE EFFECTS OF CIMETIDINE IN MOUSE BONE-MARROW CELLS EXPOSED TO GAMMA-RAYS AS ASSAYED BY THE MICRONUCLEUS TEST

An in vivo micronucleus assay using mouse bone marrow for identifying the radioprotective effect of cimetidine is described. The influence o f cimetidine, an antagonist to the histamine H2 receptor, on the kinet ics of radiation-induced micronuclei was tested in the CD-1 male mouse . Cimetidine was administered at 15 mg/kg i.p.2h prior to irradiation of mouse given various doses of gamma-rays from 0.25 to 1 Gy. The freq uency of micronucleated polychromatic erthyrocytes (PCEs) and normochr omatic erythrocytes (NCEs) per 1500 PCEs were determined at 36, 48 and 72 h post-irradiation. The results obtained indicate a linear dose re sponse for three sampling times, and that cimetidine reduces the numbe r of micronuclei in both PCE and NCE at all sampling times, as well as reducing radiation cytotoxicity. When the overall effects of radiatio n alone or in the presence of cimetidine are compared, a dose reductio n factor (DRF) of 1-5 was found for cimetidine in the dose range used in this study, which is statistically highly significant (p < 0.001). This DRF at the low dosage of cimetidine used in this study compared w ith known radioprotectors is very promising and it might be useful as a potent radioprotector. The mechanism by which cimetidine reduces cla stogenic effects of radiation is not well understood. We propose that it might act by a radical scavenging mechanism via enzyme catalysis.