Verapamil contributes to the clastogenic effects of acrylamide, cyclophosphamide, and dioxidine on somatic cells of BALB/C and C57BL/6 mice

The chromosome aberration assay of metaphase bone marrow cells was used to study the clastogenic effects of acrylamide, cyclophosphamide, dioxidine, a nd their combinations with Verapamil (a calcium antagonist) in male BALB/C and C57BL/6 mice. Verapamil gavage at single (5 mg/kg) and repeated doses ( 2.5 and 5 mg/kg five times at 24-h intervals) significantly enhanced the cl astogenic activity of acrylamide (50 and 100 mg/kg intraperitoneally) in BA LB/C mice; in C57BL/6 mice, this effect was only observed when they receive d Verapamil at doses of 2.5 mg/kg for 5 days. Verapamil administered repeat edly (2.5-10 mg, gavage) significantly increased the clastogenic activity o f cyclophosphamide (10 mg/kg intraperitoneally) in C57BL/6 mice. In BALB/C mice, this effect of Verapamil was only observed at a dose of 10 mg/kg (gav age). When injected intraperitoneally at a single dose of 0.1-0.4 mg/kg, Ve rapamil significantly enhanced the clastogenic activity of cyclophosphamide in mice of both strains. This calcium antagonist produced identical effect s when administered to BALB/C mice intraperitoneally (2.5 and 5 mg/kg) and by gavage (5 mg/kg) and to C57BL/6 mice intraperitoneally (5 and 10 mg/kg) and by gavage (2.5 mg/kg). Repeated administration of Verapamil (at all dos es tested) promoted the clastogenic effect of dioxidine (100 mg/kg intraper itoneally) on C57BL/6 mice, having no such influence on BALB/C mice. These results demonstrate the co-clastogenic activity of Verapamil in mice and su ggest that its specific manifestations depend on the dose, method, and rout e of drug administration and the genotype of test animals. (C) 1999 Elsevie r Science B.V. All rights reserved.