When mouse P815 mastocytoma cells are cultured in the presence of 1-β-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]deoxycytidinederived radioactivity into 5-methylcytosines. Analysis of DNAs by means of the bacterial restriction enzyme Hpall and its isoschizomer Mspl 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.

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This work was supported by grants from the Deutsche Forschungsgemeinschaft Dr 104/6.

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