Delayed cell cycle kinetics and chromosome aberrations induced by girostan in human peripheral blood lymphocytes...

Human peripheral blood lymphocytes (PBL) maintained in vitro for 72 hours were labeled with 5-Bromodeoxyuridine (BrdU) at 50 microliters/ml and concomitantly treated with girostan at 1.5; 2 and 2.5 micrograms/ml during the last 13; 11; 9; 7; 5 and 3 hours before cells gathering for incorporation banding analysis in metaphase spreads. Similar untreated cultures, labeled with BrdU for the same time intervals were set up as controls in order to determine the phase of cell cycle traverse in the moment when girostan was given to the cultures. When compared with controls, incorporation banding pattern in treatment samples revealed the effect induced by girostan on cell cycle kinetics during different time intervals before mitosis. Cells with entirely dark chromosomes at metaphase [were] considered in G1/G2 phase, while metaphases with a clear banding on the chromosome were presumed to be at different moments within S-phase. Connected to the observed type of banding (R or G), early S, middle S and late S-phase metaphases were identified. A dose-related delay of cell cycle traverse was induced as revealed by the increased frequency of cells that lasted in S-phase and did not reach the G2-phase. More than that, within S-phase population, an evident accumulation of cells traversing middle S-phase was observed at the same time with the decrease of cells in late S. This effect of girostan on cell kinetics is also correlated with the moment during the cell cycle traverse when cytostatic treatment is gives.(ABSTRACT TRUNCATED AT 250 WORDS)