The relationship between alkylation of specific DNA bases and induction of sister chromatid exchange

Abstract
The mechanism of induction of sister chromatid exchange (SCE) was investigated by treating Chinese hamster V-79 cells with two ethylating and two methylating mutagens at doses, taken from linear response curves, that produced 30 SCE/cell. Concentrations of the DNA alkylation products were measured or calculated at 11 DNA base sites and at the phosphodiester bond. Ethyl methanesulfonate, N-methyl-and N-ethyl-N-nitrosourea produced com-parable concentrations (3.3 to 3.5μmol product/mol DNA phosphate) of O 6 -alkyiguanine. Hence, alkyla-tion at O 6 of guanine appears relevant to SCE induction for these mutagens. Since alkylation at O 6 of guanine has been positively correlated with mutagenesis in V-79 cells, these findings support the suggestion that SCE and mutagenesis can result from a common DNA lesion. Methyl methane-sulfonate (MMS) produced very little O 6 -methyl-guanine, but did produce 3-methylthymine and 3-methyladenine, either of which might account for the MMS-induced SCE. Thus, for a series of mutagens, induction of SCE does not necessarily result from a single specific DNA lesion. Therefore, SCE can be considered a qualitative indicator of potential mutagenic events

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