Increased levels of DNA lesions induced by leucovorin-5-fluoropyrimidine in human colon adenocarcinoma.

Leucovorin augments the growth inhibitory effect of 5-fluoropyrimidines on neoplastic cells. The effect is paralleled by much higher levels of DNA fragmentation than in cells treated with 5-fluoropyrimidines alone at the same concentration. The lesions are induced by a mechanism independent of incorporation of the drug into DNA, in all probability due to reduced repair of DNA lesions induced independently of the drug treatment. Thymidine added after the treatment with fluoropyrimidines partly rescues the cells and reduces the level of DNA fragmentation.