Differential susceptibility to a mutagen among human individuals: synergistic effect on chromosome damage between bleomycin and aphidicolin.
Lymphocytes of standard human blood cultures were treated with bleomycin, aphidicolin and a combination of these two agents. A synergistic effect on chromosome damage was obvious when the two agents were used simultaneously. Various experiments showed that Aphidicolin induces chromosome breakage only in cells in the S-phase; Despite the quantitative differences in response to bleomycin among individuals, the frequency of chromatid breakages becomes high when the two agents are used together. The data suggest a differential DNA repair capacity among human subjects, since aphidicolin is known to inhibit DNA polymerase alpha, which is necessary for DNA replication and DNA repair.
D016590:Aphidicolin; D001761:Bleomycin / Q000494:pharmacology*; D002842:Chromatids / Q000648:ultrastructure; D002877:Chromosomes, Human / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D007399:Interphase
D004224:Diterpenes; D001761:Bleomycin; D016590:Aphidicolin