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© 1988 Oxford University Press

research-article

Increased O6-alkylguanine alkyltransferase activity in Chinese hamster V79 cells following selection with chloroethylating agents

John E.N. Morten 1 and Geoffrey P. Margison

Paterson Institute for Cancer Research, Christie Hospital and Holt Radium Institute Manchester M20 9BX, UK

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 µg/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 µg/ml result in specific activities of {small tilde}50 and 70 fmol/mg respectively. Only slight decreases in ATase activity were seen by 51 days after an initial selection with 10 µg/ml Mz. A similar effect was observed using chlorozotocin. Selected cells had a higher D37 for Mz (2.5–6.0 µg/ml) in comparison with control cell (D37, 0.8 µg/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.


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