The relationship between alkylation of specific DNA bases and induction of sister chromatid exchange.
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 comparable concentrations (3.3 to 3.5 micromol product/mol DNA phosphate) of O6-alkylguanine. Hence, alkylation at O6 of guanine appears relevant to SCE induction for these mutagens. Since alkylation at O6 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 methanesulfonate (MMS) produced very little O6-methylguanine, 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.
Swenson
D H
DH
The Upjohn Company, Kalamazoo, MI 49001, USA.
Harbach
P R
PR
Trzos
R J
RJ
D000477:Alkylating Agents / Q000633:toxicity*; D000478:Alkylation; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D005020:Ethyl Methanesulfonate / Q000633:toxicity; D005038:Ethylnitrosourea / Q000633:toxicity; D008741:Methyl Methanesulfonate / Q000633:toxicity; D008770:Methylnitrosourea / Q000633:toxicity; D009153:Mutagens / Q000633:toxicity*; D012854:Sister Chromatid Exchange
D000477:Alkylating Agents; D009153:Mutagens; D008770:Methylnitrosourea; D004247:DNA; D005020:Ethyl Methanesulfonate; D008741:Methyl Methanesulfonate; D005038:Ethylnitrosourea