Department of Zoology, Berhampur University, Berhampur 760007, Orissa, India.
Environ Toxicol Pharmacol. 2004 Jan;15(2-3):79-85. doi: 10.1016/j.etap.2003.10.001.
Caffeine (CAF), a widely used and extensively studied chemical, is known for the reports on its controversial and inconsistent genotoxic effects, potentiative and protective effects from the genotoxicity of chemical and physical mutagens, and its modulatory effects on the action of antineoplastic drugs. Methotrexate (MTX), an antifolate antimetabolite, is a widely prescribed antineoplastic drug with significant clastogenic effects. In the present study, in addition to the assessment of cytogenotoxicity of CAF 25, 50 or 100mg/kg in mouse bone marrow, their modulatory effects on the cytogenotoxicity of MTX 10mg/kg was assessed from the induced frequencies of aberrant metaphases, chromosomal aberrations (CAs) and percentages of dividing cells at 24h post-treatment and the induced frequency of micronuclei (MN) at 30h post-treatment. All the three doses of CAF induced higher percentages of aberrant metaphases, high frequency of CAs and MN and increased percentages of dividing cells, but the increase in the aberrant metaphases and CAs was statistically significant only with the highest dose of CAF. Thus, CAF was weakly clastogenic to mouse bone marrow cells. However, pre-treatment of each of the three doses of CAF reduced the frequency of MTX 10mg/kg-induced aberrant metaphases, CAs, MN and also the percentage of dividing cells, but significantly only by the two higher doses of CAF. Thus, the higher doses of CAF protected mouse bone marrow cells from the cytogenotoxicity of MTX. The possible mechanisms involved in bringing about the weak clastogenic action of CAF and its protection from the cytogenotoxic effects of MTX have been discussed, and bio-modulation of the effects of antineoplastic drugs has been highlighted.
咖啡因（CAF）是一种广泛使用和深入研究的化学物质，以其关于其有争议和不一致的遗传毒性作用的报告而闻名，它具有增强和保护化学和物理诱变剂遗传毒性的作用，以及对抗肿瘤药物作用的调节作用。甲氨蝶呤（MTX）是一种广泛应用的抗叶酸抗代谢物抗肿瘤药物，具有显著的断裂作用。在本研究中，除了评估 CAF 25、50 或 100mg/kg 在小鼠骨髓中的细胞遗传毒性外，还从诱导的异常有丝分裂、染色体畸变（CA）和 24 小时后处理时分裂细胞的百分比以及诱导的微核（MN）频率来评估它们对 MTX 10mg/kg 的细胞遗传毒性的调节作用 30 小时后处理。CAF 的三个剂量均诱导更高百分比的异常有丝分裂、高频率的 CA 和 MN 以及更高的分裂细胞百分比，但仅最高剂量的 CAF 使异常有丝分裂和 CA 的增加具有统计学意义。因此，CAF 对小鼠骨髓细胞具有弱断裂作用。然而，CAF 的三个剂量中的每一个预处理都降低了 MTX 10mg/kg 诱导的异常有丝分裂、CA、MN 以及分裂细胞的百分比，但仅以两种更高剂量的 CAF 显著降低。因此，CAF 的较高剂量可保护小鼠骨髓细胞免受 MTX 的细胞遗传毒性。已经讨论了导致 CAF 弱断裂作用及其对 MTX 细胞遗传毒性的保护作用的可能机制，并强调了抗肿瘤药物作用的生物调节。
