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 tested in Chinese hamster ovary (CHO) cells cultivated in vitro, with respect to its ability to induce sister chromatid exchange (SCE). The agent shows no effect on cell cycle parameters (proliferation and mitotic indices) at concentrations up to 100 microM, when administered in pulses 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 microM. A clear increase in the SCE frequency is produced starting from a concentration of 10 microM, irrespective of the treatment protocol (i.e. pulse versus continuous). This effect on the SCE frequency is maintained for as long as 10 cell cycles after removal of the agent. A partial inactivation of S-adenosyl-L-homocysteine (AdoHcy) hydrolase seems to be produced for as long as 6 h after agent removal. We suggest that under our experimental conditions ara-A exerts its action through a heritable epigenetic modification.
Perticone
P
P
Centro di Genetica Evoluzionistica del CNR, Roma, Italy.
Linguardo
M
M
Cozzi
R
R
Corbo
R M
RM
Polani
S
S
D043383:Adenosylhomocysteinase; D000818:Animals; D016466:CHO Cells; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D018095:Germ-Line Mutation; D006867:Hydrolases / Q000037:antagonists & inhibitors; D008940:Mitotic Index; D012854:Sister Chromatid Exchange; D013997:Time Factors; D014740:Vidarabine / Q000008:administration & dosage / Q000633:toxicity*
D006867:Hydrolases; D043383:Adenosylhomocysteinase; D014740:Vidarabine