Mozdarani H, Gharbali A
School of Medical Sciences, Tarbiat Modarres University, Tehran, I.R., Iran.
Int J Radiat Biol. 1993 Aug;64(2):189-94. doi: 10.1080/09553009314551291.
An in vivo micronucleus assay using mouse bone marrow for identifying the radioprotective effect of cimetidine is described. The influence of cimetidine, an antagonist to the histamine H2 receptor, on the kinetics of radiation-induced micronuclei was tested in the CD-1 male mouse. Cimetidine was administered at 15 mg/kg i.p. 2 h prior to irradiation of mouse given various doses of gamma-rays from 0.25 to 1 Gy. The frequency of micronucleated polychromatic erythrocytes (PCEs) and normochromatic erythrocytes (NCEs) per 1500 PCEs were determined at 36, 48 and 72 h post-irradiation. The results obtained indicate a linear dose response for three sampling times, and that cimetidine reduces the number of micronuclei in both PCE and NCE at all sampling times, as well as reducing radiation cytotoxicity. When the overall effects of radiation alone or in the presence of cimetidine are compared, a dose reduction 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 with known radioprotectors is very promising and it might be useful as a potent radioprotector. The mechanism by which cimetidine reduces clastogenic effects of radiation is not well understood. We propose that it might act by a radical scavenging mechanism via enzyme catalysis.
本文描述了一种利用小鼠骨髓进行的体内微核试验，以鉴定西咪替丁的辐射防护作用。在CD-1雄性小鼠中测试了组胺H2受体拮抗剂西咪替丁对辐射诱导微核动力学的影响。在给小鼠照射0.25至1 Gy的各种剂量γ射线前2小时，腹腔注射15 mg/kg西咪替丁。在照射后36、48和72小时，测定每1500个嗜多染红细胞（PCE）中微核化嗜多染红细胞（PCE）和正染红细胞（NCE）的频率。所得结果表明在三个采样时间呈线性剂量反应，并且西咪替丁在所有采样时间均减少了PCE和NCE中的微核数量，同时降低了辐射细胞毒性。当比较单独辐射或存在西咪替丁时的总体效应时，在本研究使用的剂量范围内，西咪替丁的剂量降低因子（DRF）为1.5，这在统计学上具有高度显著性（p < 0.001）。与已知的辐射防护剂相比，本研究中使用的低剂量西咪替丁的这种DRF非常有前景，它可能作为一种有效的辐射防护剂。西咪替丁降低辐射致断裂效应的机制尚不清楚。我们提出它可能通过酶催化自由基清除机制起作用。
