[Mechanism of the chromosome damaging effect of ftorafur]

Chromosome damage induced by three antineoplastic drugs -- ftuorafur (Ft), 5-fluorouracil (5-FU) and 5-fluorodeoxyuridine (FUdR) hase been studied in Djungarian hamsters cell line after 24 hours exposition with these agents before the fixation. Ft at a dose of 10 micron/ml induced aberrations in 56.7% of metaphases. 60.0% of aberrant metaphases were obtained in experiments with 0.1 micron/ml of 5 FU. FUdr at the same dose induced 24.0% of aberrant metaphases. The high frequency of chromatid breaks and gaps was typical for the mutagenic action of these fluorinated pyrimidines. The addition of Ft or 5-FU to the cell cultures 1--12 hours before fixation did not produce any significant chrosome damage, while further exposition with the drugs for 15--24 hours caused breaks in more than 50% of metaphases. Thymidine at a concentration of 1.0 micron/ml suppressed the chromosome breaking effect of Ft and 5-FU. The results obtained are in accordance with the idea that fluorodeoxyruidinemonophosphate is the ultimate mutagen for both Ft and 5-FU and that the aberrations observed are due to the lack of thymidine nucelotides caused by the former agents while DNA replication.