DNA damage by peplomycin and its repair in an in vitro system.
1. DNA damage by peplomycin, an antitumor antibiotic, and its repair by cellular enzymes were studied using pUC18 plasmid DNA. The DNA damage and repair were measured by monitoring the conformational changes of pUC18 DNA. 2. Peplomycin-induced DNA damage was enhanced by addition of ferrous ion and inhibited by deferoxamine, a specific iron chelator, suggesting iron-requirement for the DNA damage. 3. DNA damage by peplomycin was inhibited by superoxide dismutase in both native and heat-inactivated forms, possibly due to non-enzymatic interaction. 4. Peplomycin-induced, single-strand breaks in pUC18 DNA was repaired by incubating with a priming factor (an exonuclease purified from mouse ascites sarcoma cells), DNA polymerase beta, four deoxynucleoside triphosphates, T4 DNA ligase and ATP. The average repair patch size was estimated to be approximately four nucleotide length.
Zhang
B
B
Department of Biochemistry, Okayama University Medical School, Japan.
Seki
S
S
Ikeda
S
S
D000255:Adenosine Triphosphate / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects*; D011088:DNA Ligases / Q000378:metabolism; D004256:DNA Polymerase I / Q000378:metabolism; D004260:DNA Repair; D003676:Deferoxamine / Q000494:pharmacology; D003854:Deoxyribonucleotides / Q000378:metabolism; D005092:Exonucleases / Q000378:metabolism; D005296:Ferrous Compounds / Q000494:pharmacology; D016166:Free Radical Scavengers; D009690:Nucleic Acid Conformation / Q000187:drug effects; D017663:Peplomycin; D013482:Superoxide Dismutase / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D003854:Deoxyribonucleotides; D005296:Ferrous Compounds; D016166:Free Radical Scavengers; D001761:Bleomycin; D017663:Peplomycin; D000255:Adenosine Triphosphate; D013482:Superoxide Dismutase; D004256:DNA Polymerase I; D005092:Exonucleases; D011088:DNA Ligases; D003676:Deferoxamine