Limited capacity for the removal of O6-methylguanine and its regeneration in a human lymphoma line.

The Raji human lymphoma line is able to remove O6-methylguanine (O6MeG) lesions introduced by treatment of cells with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The reaction has a rapid phase in which approximately 40% of the O6MeG is removed in the first 10 min. The capacity of cells for rapid O6MeG removal is limited and is saturated at concentrations of MNNG which do not saturate the systems removing 3-methyladenine. Pretreatment of cells with MNNG inhibits their ability to remove O6MeG produced by a subsequent dose given after 2 h. Treatment with N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) is effective in diminishing cellular capacity for O6MeG removal, and cells unable to remove O6MeG and sensitive to the cytotoxic effects of MNNG are also more sensitive to ENNG than their removal competent counterparts. Regeneration of the ability to remove O6MeG requires incubation of cells for periods greater than 24 h. The O6MeG removal system is similar to that found in adapted Escherichia coli although the capacity of the Raji lymphoma line much lower than that of the induced bacteria per unit of DNA.