Release of chloroethyl ethyl sulfide-modified DNA bases by bacterial 3-methyladenine-DNA glycosylases I and II.

Treatment with chloroethyl ethyl sulfide introduces the following modified bases into DNA: 7-ethylthioethylguanine, 3-ethylthioethyladenine, and O6-ethylthioethylguanine. Using the ethylthioethylated bases as models for DNA modifications involving relatively bulky alkyl groups, we have investigated the release of these bases by Escherichia coli 3-methyladenine-DNA glycosylases I and II. 3-Methyladenine-DNA glycosylase I releases only 3-ethylthioethyladenine from chloroethyl ethyl sulfide-modified DNA, but does so at a rate which exceeds the rate of release of 3-methyladenine (m3A) from methyl nitrosourea-modified DNA under these conditions. 3-Methyladenine-DNA glycosylase II releases both 3-ethylthioethyladenine and 7-ethylthioethylguanine at rates approximating or exceeding the rate of release of m3A from methylnitrosourea-modified DNA. We conclude that these glycosylases may offer some protection against the toxicity of agents which introduce bulky groups into E. coli DNA.