In vivo protection by cimetidine against fast neutron-induced micronuclei in mouse bone marrow cells

• Published in: Cancer letters Vol. 124; no. 1; pp. 65 - 71
• Main Authors: Mozdarani, Hossein, Khoshbin-Khoshnazar, Ali R
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 13-02-1998; Elsevier
• Subjects: Animals; Biological and medical sciences; Bone marrow cells; Bone Marrow Cells - drug effects; Bone Marrow Cells - radiation effects; Carcinogenesis, carcinogens and anticarcinogens; Chemical agents; Cimetidine; Cimetidine - pharmacology; DNA - drug effects; DNA - radiation effects; DNA Damage; Fast Neutrons; Male; Medical sciences; Mice; Micronuclei; Micronuclei, Chromosome-Defective - drug effects; Micronuclei, Chromosome-Defective - radiation effects; Radiation Injuries, Experimental - etiology; Radiation Injuries, Experimental - prevention & control; Radiation-Protective Agents - pharmacology; Radioprotection; Tumors; Bone marrow cells; Radioprotection; Fast neutrons; Micronuclei; Cimetidine; Intraperitoneal administration; Rodentia; Vertebrata; Ionizing irradiation; Mammalia; Treatment; Mouse; Animal; Micronucleus; Tumor progression; Bone marrow; Fast neutron
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(97)00451-5

We have previously shown that cimetidine is capable of reducing the clastogenic effect of
γ-rays. In this research the radioprotective property of this drug was examined against low doses of fast neutrons using the miconucleus assay. Swiss albino male mice (12 weeks old) were irradiated by fast neutrons emitted from a
241Am-
9Be source. The absorbed doses were 1.5, 2.25, 3.375 and 5.06 cGy at a dose rate of 0.718 cGy/h. Two hours prior to neutron irradiation mice were treated by cimetidine at a concentration of 15 mg/kg body weight injected i.p. Mice were sacrificed by cervical dislocation at different post-irradiation times (24, 48 and 72 h). The results obtained show that the frequency of neutron-induced micronuclei in polychromatic erythrocytes (PCEs) is significantly higher than those of control groups (
P<0.05) at the neutron doses used in these experiments. Moreover, cimetidine effectively reduced (1.5–2-fold) the frequency of micronuclei in PCE (
P<0.05). These results show that cimetidine can protect bone marrow cells against clastogenic effects of low dose fast neutrons and hence high linear energy transfer (LET) radiation. The mechanism by which cimetidine reduces the clastogenic effects of fast neutrons is not fully understood. It might act through a free radical scavenging mechanism associated with the amplification of the glutathione system.