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Radioprotective properties of histamine H2 receptor antagonists: present and future prospects.

Various chemical agents were examined for their radioprotective capability to provide partial protection against radiation injury over the past 50 years. However, no suitable drug has yet been introduced for routine clinical use. In the present study, the radioprotective potential of H2 receptor antagonists was examined in in vivo and in vitro conditions. For this purpose, an in vivo micronucleus assay and an in vitro metaphase analysis were used to test the effects of cimetidine, ranitidine, and famotidine on radiation-induced clastogenic effects. For micronuclei assay, BALB/c mice were irradiated in the presence or absence of drugs, and slides were prepared from bone marrow cells. The frequency of micronuclei was determined in bone marrow erythrocytes. For the in vitro assay, lymphocytes in whole peripheral blood were exposed to radiation in the presence or absence of drugs, and the frequency of chromosomal aberrations were determined. The results show that radiation produced a high number of micronuclei in polychromatic erythrocytes (PCE) and chromosomal aberrations in lymphocytes. All three drugs used in this study effectively reduced the frequency of radiation-induced micronuclei and chromosomal aberrations at various doses. Famotidine was found to be more effective than the other two drugs. From the results obtained, it can be concluded that H2-receptor antagonists reduced the clastogenic effects of radiation with a dose reduction factor (DRF) of 1.5-2 in vivo and in vitro. The way in which these drugs reduce the clastogenic effects of radiation might be via a radical scavenging mechanism.