Inhibitors of topoisomerases do not block the passage of human lymphocyte chromosomes through mitosis.
Cultured human lymphocytes have been treated with a number of topoisomerase inhibitors, to see whether topoisomerase II is involved in the process of chromosome segregation at anaphase. Results were assessed by examination of cytogenetical preparations of spread chromosomes. Four effects were observed, although no inhibitor produced all four effects. These effects were: inhibition of entry into mitosis; chromosome breakage and rearrangement; inhibition of chromosome condensation; and inhibition of chromosome segregation. Evidence for the last was ambiguous. Although there was evidence that separation of chromatids was affected when cells were treated with colchicine as well as topoisomerase II inhibitors (most notably with nalidixic acid, which resulted in complete fusion of the chromatids), no evidence was obtained to show that, in the absence of colchicine, cells treated with inhibitors could not proceed through anaphase normally. The topoisomerase I inhibitor, camptothecin, differed from the topoisomerase II inhibitors in not showing any effect on chromosome condensation or any significant effect on segregation.
Sumner
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MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.
D000677:Amsacrine / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D004264:DNA Topoisomerases, Type I / Q000502:physiology; D004250:DNA Topoisomerases, Type II / Q000502:physiology; D003630:Daunorubicin / Q000494:pharmacology; D004611:Ellipticines / Q000494:pharmacology; D004996:Ethidium / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D008938:Mitosis / Q000187:drug effects / Q000502:physiology*; D008942:Mitoxantrone / Q000494:pharmacology; D009268:Nalidixic Acid / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
D004611:Ellipticines; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D000677:Amsacrine; C034192:ellipticine; D009268:Nalidixic Acid; D005047:Etoposide; D008942:Mitoxantrone; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; D004996:Ethidium; D002166:Camptothecin; D003630:Daunorubicin