3-Methyladenine DNA glycosylase activity in a glial cell line sensitive to the haloethylnitrosoureas in comparison with a resistant cell line.
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 alkyl-transferase, suggesting that both enzyme activities may be involved in the resistance of this cell line to the haloethylnitrosoureas.
Matijasevic
Z
Z
Department of Pharmacology, University of Massachusetts Medical School, Worcester 01655.
Bodell
W J
WJ
Ludlum
D B
DB
D004247:DNA / Q000378:metabolism; D045647:DNA Glycosylases; D004351:Drug Resistance; D005038:Ethylnitrosourea / Q000494:pharmacology*; D005910:Glioma / Q000378:metabolism; D009699:N-Glycosyl Hydrolases / Q000032:analysis*; D014407:Tumor Cells, Cultured
D004247:DNA; C021565:3-methyladenine-DNA glycosylase; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D005038:Ethylnitrosourea