Progressive formation of DNA lesions during treatment with anti-metabolites without incorporation of the drugs into DNA.
Anti-metabolites, such as methotrexate, 5-fluoropyrimidines or hydroxyurea, induce progressive formation of DNA lesions. 5-Fluoropyrimidines induce DNA lesions either by incorporation of the drug into DNA or by a mechanism not involving incorporation. The second mechanism, not involving incorporation, is also seen with methotrexate and hydroxyurea. The three anti-metabolites have in common their ability to reduce intracellular levels of nucleotides, resulting in reduced efficiency of repair of DNA lesions. The lesions probably appear spontaneously, independently of the drug treatment.
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Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
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D016590:Aphidicolin; D004249:DNA Damage; D004260:DNA Repair; D004224:Diterpenes / Q000494:pharmacology; D005467:Floxuridine / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured
D004224:Diterpenes; D005467:Floxuridine; D016590:Aphidicolin; D013940:Thymidylate Synthase