PERSISTENCE OF SISTER-CHROMATID EXCHANGE BY 9-BETA-D-ARABINOFURANOSYLADENINE IN CHINESE-HAMSTER OVARY CELLS CULTIVATED IN-VITRO

The cytogenetic activity of 9-beta-D-arabinofuranosyladenine (ara-A), a known antitumor agent with an unknown mechanism of action (possibly acting via demethylation and/or decrease in DNA synthesis), has been t ested in Chinese hamster ovary (CHO) cells cultivated in vitro, with r espect to its ability to induce sister chromatid exchange (SCE). The a gent shows no effect on cell cycle parameters (proliferation and mitot ic indices) at concentrations up to 100 muM, when administered in puls es ranging from 3 to 12 h. Furthermore, even if administered over the entire treatment period (24 h), a severe cell cycle delay appears only at a concentration of 100 muM. A clear increase in the SCE frequency is produced starting from a concentration of 10 muM, irrespective of t he treatment protocol (i.e. pulse versus continuous). This effect on t he SCE frequency is maintained for as long as 10 cell cycles after rem oval of the agent. A partial inactivation of S-adenosyl-L-homocysteine (AdoHcy) hydrolase seems to be produced for as long as 6 h after agen t removal. We suggest that under our experimental conditions ara-A exe rts its action through a heritable epigenetic modification.