Potentiation by caffeine of the frequencies of micronuclei induced by mitomycin C and cyclophosphamide in young mice

Abstract

Employing the micronucleus test in mouse bone marrow and in fetal mouse liver, the possible clastogenicity of caffeine as well as its influence on MMC- and CP-induced micronucleus levels were studied. The treatment of male and female C57B1 or BDF 1 (C57B1 × DBA2) mice with caffeine (1 or 3 × mg/kg and 100 mg/kg, s.c.) had no clastogenic effect in mouse bone marrow or in the fetal livers and maternal bone marrow when pregnant mice were injected with caffeine on day 16–17 of gestation. MMC (2.0 mg/kg, i.p.) increased up to 10–30-fold the number of MNPCEs in bone marrow compared to a 3–7 fold elevation of MNPCEs in fetal liver. A similar effect was also established in pregnant mice treated with CP (30 mg/kg, i.p.). No significant sex differences in spontaneous and MMC- or CP-induced MNPCEs levels were established in C57B1 and BDF 1 mice. However, a significantly higher spontaneous rate of MNPCEs as well as a better-expressed responsiveness to the clastogenic activity of MMC and CP were established in C57B1 compared to BDF 1 mice. The pregnancy had no effect on MMC- or CP-induced clastogenicity although a tendency to a decreased sensitivity to the damaging activity of MMC seemed to be detected in pregnant C57B1 mice compared to virgin female animals. The combined treatment of mice with caffeine (3 × 100 mg/kg) and MMC or CP caused an up to 45–49% potentiation of clastogenesis in the bone marrow of male, female and pregnant female C57B1 and BDF 1 mice but not in fetal mouse livers.