The production of chromosomal alterations in human lymphocytes by drugs known to interfere with the activity of DNA topoisomerase II. I. m-AMSA

Publisher Website
Google Scholar
Abstract
The frequencies of chromosomal aberrations and sister chromatid exchanges (SCE) were studied in human peripheral lymphocytes after exposure of whole blood cultures to the antitumour agent m-AMSA. Chromosome-type aberrations were found in cells exposed before stimulation or during the G1-phase of the cell cycle. Chromatid-type aberrations were obtained in cells exposed during the S- and G2-phases, but also in cells exposed in the G1-phase or before stimulation. Treatment of lymphocytes with m-AMSA in the G1-phase or before stimulation had the additional effect of strongly increasing the frequency of SCE. When unstimulated lymphocytes were exposed to m-AMSA, the frequencies of SCE and chromatid-type aberrations, but not the frequency of chromosome-type aberrations, could be strongly reduced by holding the cells in F-10 for 2–4 h before stimulation, or by changing the growth medium after stimulation. A 1-h incubation in growth medium was sufficient for obtaining this reduction. The medium in which the m-AMSA-treated cells were incubated for the first 3 h after stimulation proved to be capable of inducing chromatid-type aberrations in late S/G2-phase and SCEs in the S-phase. These observations show that the chromatid-type aberrations and SCEs obtained by exposing unstimulated lymphocytes to m-AMSA were not produced during the treatment itself, but after stimulation at an advanced stage of the cell cycle by an active substance (m-AMSA or a metabolite of m-AMSA) released into the medium during the first hours of incubation. Post-treatments in G2 with 1-β-D-arabinofuranosylcytosine (ara-C) and hydroxyurea strongly enhanced the frequency of chromatidtype aberrations obtained after treatment of stimulated or unstimulated lymphocytes with m-AMSA. Post-treatments in unstimulated or G1-phase lymphocytes with ara-C did not influence the frequency of chromosome-type aberrations induced by m-AMSA at these stages, but strongly enhanced those induced by X-rays.

This publication has 25 references indexed in Scilit: