Nature of chromosome aberrations induced in pre-DNA- synthesis period in human leukocytes by daunomycin

Abstract

Chromosomes from human leukocytes cultured in vitro were exposed to anti- leukemic antibiotic daunomycin during G 0 and G 1 periods of interphase. Chromosomal aberrations were rare or absent in cells treated with up to 0.15 μg/ml of the drug during the first 12 h of culture initiations indicating the relative insensitivity of the cells during early part of G 1 to the concentrations studied. All types of aberrations (chromosome and chromatid types of breaks and exchanges) were observed in cells treated between 12–16 h of culture and later. The data indicate that reunions take place in absence of detectable DNA synthesis and thus perhaps depend upon protein synthesis. The presence of chromatid types of exchanges in cells treated before initiation of S phase is explained on the basis of chromosome aberrations being translated into chromatid-type aberrations or resolution of unreplicated G 1 structure of chromosomes into functional two-stranded by “loosening” of the bonds holding the two sister structures together. A new type of chromosome aberration, monocentric triradials—apparently originating by the manipulation of a single chromosome—is described in relation to chromosome-type aberrations being translated into chromatid- type aberrations.