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

Abstract

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), methyl-methane sulfonate (MMS) or ethylmethane sulfonate (EMS) treatment. Incubation with MNNG (10 .mu.M) first depletes the methyltransferase activity, then the number of methyltransferase molecules per cell increases and reaches .apprx. 3-fold the constitutive level after 48 h. Incubations with MMS (0.5 or 1 mM) or with EMS (5 or 10 mM) did not modify or partially decrease the constitutive methyltransferase level. However, an enhancement of the activity is also observed after 48 h: the activity is 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.