1-beta-D-arabinosyl-5-azacytosine. Cytocidal activity and effects on the synthesis and methylation of DNA in human colon carcinoma cells.

The cytocidal activity of arabinosyl-5-azacytosine (araAC) and its effect on the synthesis and methylation of DNA in the human colon carcinoma cell line HT-29 was examined and compared with three other cytidine analogues. Treatment for 2 hr with 10(-6)M arabinosylcytosine (araC), araAC, 5-azacytidine (AZC), or 2'-deoxy-5-azacytidine (dAZC) produced a 7-30% reduction in cell viability. Prolongation of drug exposure to 24 hr significantly enhanced the cytotoxicity of all analogues, and particularly dAZC. AZC and dAZC were potent inhibitors of DNA methylation in the absence of inhibition of DNA synthesis, whereas araC and araAC primarily affected DNA synthesis. RNA synthesis was not affected by any of the analogues. dAZC and AZC were incorporated into DNA to a greater extent than were araC or araAC upon short- and long-term drug exposure, whereas only AZC was incorporated into RNA. These data indicate that araAC appears to behave more as an analogue of araC rather than of dAZC or AZC, wherein it produces rapid inhibition of DNA synthesis and is incorporated into DNA.