EFFECT OF PREINDUCTION OF METALLOTHIONEIN SYNTHESIS ON CLASTOGENICITY OF ANTICANCER DRUGS IN MICE

The effect of pretreatment with metallothionein (MT) inducers (bismuth nitrate or zinc chloride) on clastogenicity of anticancer drugs was investigated. Bismuth nitrate (50 mu mol/kg) or zinc chloride (400 mu mol/kg) was administered s.c. to mice once a day for two days prior to treatment with 3.3 mu mol/kg of cis-diamminedichloroplatinum(II) (cis-DDP), 3.4 mu mol/kg of adriamycin (ADR), 72 mu mol/kg of cyclophosphamide (CPA) or 0.41 mu mol/kg of L-phenylalanine mustard (L-PAM). The frequency of occurrence of erythrocytes with micronuclei in bone marrow was increased by each anticancer drug at 24 h after treatment. Micronucleus formation was significantly prevented by pretreatment with either bismuth nitrate or zinc chloride. MT concentration in bone marrow cells of mice at the time of treatment with anticancer drugs increased to 2- and 3.5-fold by pretreatment with bismuth nitrate and zinc chloride, respectively. These results indicate that MT induction in bone marrow cells effectively prevents micronucleus induction of anticancer drugs.