Interactions of the UVRABC endonuclease in vivo and in vitro with DNA damage produced by antineoplastic anthracyclines.
The anthracycline antineoplastic agents Adriamycin and N-trifluoroacetyl-Adriamycin-14-valerate were assayed in vivo and in vitro for ability to produce DNA lesions recognized by the UVRABC endonuclease, a DNA repair enzyme of Escherichia coli which recognizes large, bulky lesions in DNA. We found that, while both drugs produce DNA lesions, only the lesions produced by Adriamycin were toxic. Hence, anthracycline antineoplastic activity may be related to production of large, bulky lesions in DNA, while toxicity may correlate with toxicity measured in a simple E. coli DNA repair mutant test system.
D004260:DNA Repair; D004261:DNA Replication / Q000187:drug effects*; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000633:toxicity*; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D029968:Escherichia coli Proteins; D007700:Kinetics; D009154:Mutation
D029968:Escherichia coli Proteins; C016163:valrubicin; D004317:Doxorubicin; D004706:Endodeoxyribonucleases; C036385:endodeoxyribonuclease uvrABC