Increased O6-alkylguanine alkyltransferase activity in Chinese hamster V79 cells following selection with chloroethylating agents.
Chinese hamster V79 lung fibroblasts express low levels (specific activity 2-4 fmol/mg protein) of O6-alkylguanine (O6-AG) alkyltransferase (ATase). In cells surviving selection with low doses (10 micrograms/ml) of the chloroethylating agent, mitozolomide (Mz), ATase activity was increased 5- to 8-fold. Repeated selection of such cells produced a maximal specific activity of 36-40 fmol/mg protein, whilst selection at 20 or 40 micrograms/ml result in specific activities of approximately 50 and 70 fmol/mg respectively. Only slight decreases in ATase activity were seen by 51 days after an initial selection with 10 micrograms/ml Mz. A similar effect was observed using chlorozotocin. Selected cells had a higher D37 for Mz (2.5-6.0 micrograms/ml) in comparison with control cell (D37, 0.8 micrograms/ml) but the D37s for nitrogen mustard and vincristine were closely similar in selected and control cells. Possible explanations for the increase in ATase activity are discussed.
Morten
J E
JE
Paterson Institute for Cancer Research, Christie Hospital and Holt Radium Institute, Manchester, UK.
Margison
G P
GP
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D005786:Gene Expression Regulation / Q000187:drug effects; D008168:Lung / Q000201:enzymology; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology*; D019853:O(6)-Methylguanine-DNA Methyltransferase; D014162:Transfection
D009588:Nitrogen Mustard Compounds; C040369:mitozolomide; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase