ANTIGENOTOXIC EFFECTS OF CIMETIDINE AGAINST BENZENE INDUCED MICRONUCLEI IN MOUSE BONE-MARROW ERYTHROCYTES

An in vivo micronucleus assay using Balb/C male mice was used to exami ne antigenotoxic effects of cimetidine (CM) on benzene (BZN) induced g enotoxic effects. CM not only has therapeutic and immunomudolatory rol e, but it has also been shown to protect bone marrow stem cells from r adiation induced clastogenic effects. Therefore, in the present study we attempt to investigate the protective effects and possible mechanis ms involved in the effects of CM. An 8-week-old wale Balb/C mice (22 /- 4 g weight) were treated with different doses of BZN (400, 600 and 800 mg/kg body weight), i.p. and sampled at 24, 48 and 72 h after trea tment by cervical dislocation. Various doses of CM (10, 15, 30 mg/kg) were used in association with BZN and 1-2 h prior to BZN treatment. Re sults show that BZN effectively induced micronuclei in polychromatic e rythrocytes (PCEs). Application of CM led to a significant reduction o f micronuclei in PCEs, i.e. 2-fold after 10 mg/kg and 3-fold after 30 mg/kg CM treatment. Results also indicate CM was more effective when u sed in combination with BZN. Therefore, results indicate that CM could reduce clastogenic effects of BZN. Although further investigations ar e needed to reveal the mechanistical background behind the effect, the most probable mechanism involved might be free radical scavenging. Th is mechanism might be associated with amplification of glutathione sys tem and cytochrome P-450 inhibition. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.