MUTAGENICITY OF 5-AZACYTIDINE AND RELATED NUCLEOSIDES IN C3H-10T1/2 CLONE-8 AND V79 CELLS

Google Scholar
  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (3) , 817-823
Abstract
To determine whether 5-azacytidine (5-AzaCR) [a cancer chemotherapeutic nucleoside]-induced transformation and/or differentiation of C3H/10T1/2 clone 8 (10T1/2) [mouse embryo fibroblast] cells might have a mutational basis, whether 5-AzaCR and structurally related nucleoside analogs could mutate 10T1/2 and Chinese hamster V79 [lung fibroblast] cells was studied. In an assay for mutation to ouabain resistance in 10T1/2 cells, which detects base substitution mutations but not frameshift mutations, 5-AzaCR and 6-azacytidine were not significantly mutagenic. 5-Aza-2''-deoxycytidine, 5-fluoro-2''-deoxycytidine, 5,6-dihydro-5-azacytidine, 5-fluoro-2''-deoxyuridine (FUdR), 5-bromo-2''-deoxyuridine (BUdR) and 1-.beta.-D-arabinofuranosylcytosine (ara-C) were only weakly mutagenic. In an assay for mutation to ouabain resistance in V79 cells, which also detects base substitution mutations but not frameshift mutations, 5-AzaCR, 5-aza-2''-deoxycytidine, FUdR and ara-C were not detectably mutagenic and BUdR was moderately mutagenic at highly cytotoxic concentrations. In an assay for mutation to 8-azaguanine resistance in V79 cells, which detects base substitution and frameshift mutations, 5-fluoro-2''-deoxycytidine and ara-C were weakly mutagenic, BUdR was moderately mutagenic at very cytotoxic concentrations, and 5-AzaCR, 5-aza-2''-deoxycytidine, FUdR, 6-azacytidine and 5,6-dihydro-5-azacytidine were not significantly mutagenic. Therefore, 5-AzaCR and related cytosine analogs can be considered as negligibly mutagenic. This study does not provide support for a mutational basis for 5-AzaCR-induced differentiation in 10T1/2 cells. There was no correlation between the mutagenicity of the nucleosides 5-AzaCR, ara-C, BUdR and FUdR studied here and their previously reported abilities to transform 10T1/2 cells. The mutagenicities of 5-AzaCR and FUdR were so low that the biological significance of these effects is uncertain. It is not clear to what extent, if any, mutation contributes to the transformation caused by these 2 compounds, and other possible mechanisms of transformation should also be investigated.