Modulatory effects of caffeine on methotrexate-induced cytogenotoxicity in mouse bone marrow

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.