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 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 ˜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.