Micronucleus induction in mouse peripheral blood reticulocytes by 2,7-diaminophenazine and related compounds

The peripheral blood micronucleus test using acridine orange (AO) supravital staining was performed with phenazine (Pz), 1-aminophenazine (1-APz), 2-aminophenazine (2-APz) and 2,7-diaminophenazine (2,7-DAPz). Male ICR mice and BDF1 mice were treated intraperitoneally once or twice 24 h apart with each chemical. Irrespective of the number of administrations, Pz and 1-APz were not clastogenic in either mouse strain. In the single treatment regime, 2-APz slightly increased micronucleated reticulocytes (MNRETs) 48 h after 200 mg/kg dosing in ICR mice and 72 h after 400 mg/kg dosing in BDF1 mice. The MNRET frequencies were not enhanced after double treatment in either mouse strain. The single treatment with 2,7-DAPz strongly and dose-dependently induced MNRETs in BDF1 mice, and the incidences of MNRETs, which peaked 48 or 72 h after treatment, were much higher than those in ICR mice. In both mouse strains, the frequencies of MNRETs observed after double treatment with 2,7-DAPz were higher than those after single treatment. The MNRET incidence induced 72 h after first 200 mg/kg dosing in BDF1 mice was 2.21%.