Blagoeva P M, Balansky R M, Mircheva T J
Laboratory of Chemical Mutagenesis and carcinogenesis, National Center of Oncology, Sofia, Bulgaria.
Mutat Res. 1991 Jan;246(1):123-7. doi: 10.1016/0027-5107(91)90114-4.
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.
采用小鼠骨髓微核试验和胎鼠肝脏微核试验，研究了咖啡因可能的致断裂性及其对丝裂霉素C（MMC）和环磷酰胺（CP）诱导的微核水平的影响。用咖啡因（1或3×50mg/kg和100mg/kg，皮下注射）处理雄性和雌性C57Bl或BDF1（C57Bl×DBA2）小鼠，在小鼠骨髓、胎鼠肝脏以及妊娠小鼠妊娠第16 - 17天注射咖啡因时的母鼠骨髓中均未发现致断裂作用。与胎鼠肝脏中微核多染红细胞（MNPCEs）数量升高3 - 7倍相比，MMC（2.0mg/kg，腹腔注射）使骨髓中MNPCEs数量增加了10 - 30倍。在用CP（30mg/kg，腹腔注射）处理的妊娠小鼠中也观察到了类似的效果。在C57Bl和BDF1小鼠中，自发的以及MMC或CP诱导的MNPCEs水平均未发现明显的性别差异。然而，与BDF1小鼠相比，C57Bl小鼠中MNPCEs的自发率显著更高，并且对MMC和CP的致断裂活性反应更明显。妊娠对MMC或CP诱导的致断裂性没有影响，尽管与未孕雌性动物相比，妊娠C57Bl小鼠似乎对MMC的损伤活性敏感性有降低的趋势。咖啡因（3×100mg/kg）与MMC或CP联合处理雄性、雌性和妊娠雌性C57Bl及BDF1小鼠，可使骨髓中的断裂效应增强45 - 49%，但对胎鼠肝脏无此作用。
