Antitumour imidazotetrazines XXVIII 3-methyladenine DNA glycosylase activity in cell lines sensitive and resistant to temozolomide.
The ability of extracts of a range of cell lines to release methylated bases from a DNA substrate, which had been modified with [3H]dimethyl sulphate, has been compared in cell lines with differing sensitivity to the cytotoxic drug, temozolomide. High performance liquid chromatography profiles of the bases released by these extracts showed that the activity was specific for 3-methyladenine. There was little variation in the level of 3-methyladenine-DNA glycosylase between the different cell lines despite a 40-fold difference in sensitivity to temozolomide and no correlation with the level of O6-alkylguanine-DNA alkyltransferase.
Deans
B
B
Pharmaceutical Sciences Institute, Aston University, Birmingham, UK.
Tisdale
M J
MJ
D000230:Adenocarcinoma; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002051:Burkitt Lymphoma; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms; D045647:DNA Glycosylases; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000302:isolation & purification / Q000378:metabolism; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004351:Drug Resistance / Q000502:physiology; D006801:Humans; D007700:Kinetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D008175:Lung Neoplasms; D051379:Mice; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D013463:Sulfuric Acid Esters / Q000378:metabolism; D000077204:Temozolomide
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D013463:Sulfuric Acid Esters; D003606:Dacarbazine; C021565:3-methyladenine-DNA glycosylase; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; C007482:dimethyl sulfate; D000077204:Temozolomide