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3-Methyladenine DNA Glycosylase Activity in a Glial Cell Line Sensitive to the Haloethylnitrosoureas in Comparison with a Resistant Cell Line¹

Department of Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 06155 [Z. M., D. B. L.], and Brain Tumor Research Center of the Department of Neurological Surgery, University of California, San Francisco, California 94143 [W. J. B.]

Extracts of a glial cell line (SF-126) which is sensitive to the cytotoxic effect of the haloethylnitrosoureas and of a cell line (SF-188) which is resistant to these agents have been tested for their ability to release methylated bases from a DNA substrate which has been modified with [³H]dimethyl sulfate. In comparison with the sensitive cell line, extracts from the resistant cell line have 2–3-fold higher enzymatic activity. High performance liquid chromatography profiles of the bases which are released by these extracts show that the activity is specific for 3-methyladenine, suggesting that the resistant cells contain elevated levels of 3-methyladenine DNA glycosylase. Previous studies have shown that these cells also contain elevated levels of O⁶-alkylguanine-DNA alkyltransferase, suggesting that both enzyme activities may be involved in the resistance of this cell line to the haloethylnitrosoureas.

¹ Supported by Grants CA44499 and CA13525 from the National Cancer Institute.

² To whom requests for reprints should be addressed.

Received 12/ 5/90. Accepted 1/17/91.

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