Elevated level of enzymatic DNA methylation in cells treated with 1-beta-D-arabinofuranosylcytosine

When mouse P815 mastocytoma cells are cultured in the presence of 1-beta-D-arabinofuranosylcytosine (ara-C), a dose-dependent inhibition of cell proliferation and DNA synthesis can be observed. The DNA synthesized in the presence of ara-C is more highly enzymatically methylated than that of controls as measured by conversion of incorporated [14C]deoxycytidine-derived radioactivity into 5-methylcytosines. Analysis of DNAs by means of the bacterial restriction enzyme HpaII and its isoschizomer MspI revealed an aberrant DNA methylation pattern after ara-C treatment. The hypermethylation of DNA persisted also in the cell cycle following the treatment in the absence of ara-C. No such changes in DNA methylation patterns following ara-C treatment were observed in P815/ara-C, a subclone of P815 cells resistant to ara-C.