The O6-methylguanine-DNA-methyltransferase activity of rat hepatoma cells is increased after a single exposure to alkylating agents.

The O6-methylguanine-DNA-methyltransferase activity was measured in rat hepatoma cells (H4 cells) at different times after N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), methylmethane sulfonate (MMS) or ethylmethane sulfonate (EMS) treatment. Incubation with MNNG (10 microM) first depletes the methyltransferase activity, then the number of methyltransferase molecules per cell increases and reaches approximately 3-fold the constitutive level after 48 h. Incubations with MMS (0.5 or 1 mM) or with EMS (5 or 10 mM) do not modify or partially decrease the constitutive methyltransferase level. However, an enhancement of the activity is also observed after 48 h: the activity in 5- and 4-fold higher than the control value in MMS- and EMS-treated cells, respectively. The methyltransferase increase is due to de novo protein synthesis. It is not observed in cells constitutively lacking this protein. The data suggest that the O6-methylguanine (O6-meGua) repair capacity of H4 cells can be increased after a single treatment with alkylating agents, by a process different to the adaptive response.