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

Mutat Res. 1991 Jan;246(1):123-7. doi: 10.1016/0027-5107(91)90114-4.

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 C57Bl or BDF1 (C57Bl x DBA2) mice with caffeine (1 or 3 x 50 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 C57Bl and BDF1 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 C57Bl compared to BDF1 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 C57Bl mice compared to virgin female animals. The combined treatment of mice with caffeine (3 x 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 C57Bl and BDF1 mice but not in fetal mouse livers.

MeSH terms

  • Alkylating Agents / pharmacology*
  • Animals
  • Caffeine / pharmacology*
  • Cyclophosphamide / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Erythrocytes / drug effects
  • Female
  • Humans
  • Liver / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Micronuclei, Chromosome-Defective / drug effects
  • Micronucleus Tests
  • Mitomycin
  • Mitomycins / pharmacology*
  • Pregnancy

Substances

  • Alkylating Agents
  • Mitomycins
  • Caffeine
  • Mitomycin
  • Cyclophosphamide