Enhancement of methotrexate-induced growth inhibition, cell killing and DNA lesions in cultured L5178Y cells by the reduction of DNA repair efficiency.

Acute treatment of L5178Y cells by methotrexate (MTX) caused concentration-dependent post-treatment growth inhibition and cell killing. The effects were potentiated in the presence of caffeine (CAF). At the same experimental conditions the CAF-dependent increase in mature and newly formed DNA lesions was found. The results suggest that even short MTX treatment can cause DNA lesions which are normally, at least partially, repaired. By the reduction of DNA repair efficiency with CAF, these lesions can be expressed what finds its reflection in the enhancement of MTX cytotoxicity.