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Chromosome aberrations induced in human leukocytes by the antileukemic antibiotic adriamycin.
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1971
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CytogeneticsImmunologyPathologyPharmacotherapySister DrugAntimicrobial ChemotherapyDrug ResistanceHematological MalignancyHematologySelective ToxicityChromosome AberrationsAntimicrobial ResistanceAntileukemic Antibiotic AdriamycinHealth SciencesAntimicrobial PharmacokineticsPharmacologyCell BiologyAntibioticsChromosomal DamageAntimicrobial PharmacodynamicsMedicineHuman Leukocytes
Summary A new antitumor, antileukemic antibiotic-adriamycin-is shown to cause chromosomal damage when used on human leukocytes in in vitro cultures at concentrations as low as 0.02 μg/ml for 24 hr or 0.05, 0.10, or 0.15 μg/ml for 3 to 4 hr. Aberrations of all conceivable types (intra- as well as inter-chromatid, -chromosome, and chromatid-chromosome type) are observed. However, a high frequency of chromosome-type fragments is noticed which compares in general with the frequency of chromatid-type exchanges but is higher than the chromatid-type breaks. Asymmetrical exchanges are more frequent than symmetrical ones. The distribution of exchange points along the length of chromosome (or group of chromosomes) expresses nonrandom effect of adriamycin on the chromatin matter. Chromosomes 3 and Y appear to be far more resistant to the effect of the drug than other chromosomes. An analysis of fragments and exchanges indicates nonrandomness of the action of the drug within chromosomes also. Study of exchanges involving corresponding points of the members of the exchange complex show that adriamycin perhaps does not induce somatic crossing over to any considerable extent. These observations agree with those made on a sister drug, daunomycin (daunorubicin).