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, and 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 clastogenic activity of acrylamide (50 and 100 mg/kg intraperitoneally) in BALB/C mice; in C57BL/6 mice, this effect was only observed when they received Verapamil at doses of 2.5 mg/kg for 5 days. Verapamil administered repeatedly (2.5-10 mg, gavage) significantly increased the clastogenic activity of 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 (gavage). When injected intraperitoneally at a single dose of 0.1-0.4 mg/kg, Verapamil significantly enhanced the clastogenic activity of cyclophosphamide in mice of both strains. This calcium antagonist produced identical effects 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 doses tested) promoted the clastogenic effect of dioxidine (100 mg/kg intraperitoneally) on C57BL/6 mice, having no such influence on BALB/C mice. These results demonstrate the co-clastogenic activity of Verapamil in mice and suggest that its specific manifestations depend on the dose, method, and route of drug administration and the genotype of test animals.
Nesterova
E V
EV
Research Institute of Pharmacology, Russian Academy of Medical Sciences, Baltiiskaya Str. 8, Moscow, 125315, Russian Federation.
Durnev
A D
AD
Seredenin
S B
SB
D020106:Acrylamide / Q000633:toxicity*; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000633:toxicity*; D002869:Chromosome Aberrations / Q000235:genetics*; D003520:Cyclophosphamide / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D011810:Quinoxalines / Q000633:toxicity*; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D009153:Mutagens; D011810:Quinoxalines; C001077:dioxidine; D020106:Acrylamide; D003520:Cyclophosphamide; D014700:Verapamil