MNNG-induced partial phenotypic reversion of Mer- cells

The effect of pretreatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on MNNG sensitivity of the surviving population was compared in two HeLa lines, one of the Mer+ phenotype (HeLa S3) and one of the Mer- phenotype (HeLa MR). Whereas MNNG pretreatment of HeLa Mer+ cells had no effect on the MNNG sensitivity of surviving cells, Mer- cells surviving a first exposure to MNNG became much more resistant to MNNG. Comparison of the sensitivity of individual HeLa MR clones with their MNNG-pretreated population and analysis of the composition of the pretreated population showed that the majority of cells surviving the MNNG pretreatment now displayed the Mer+ phenotype in respect to sensitivity to MNNG. One MNNG-resistant clone derived from a pretreated HeLa MR population (Cl 4) was characterized further. It had a similar sensitivity to the Mer+ line to all monofunctional alkylating agents, but was as sensitive as the Mer- line to the crosslinking agent chloroethylnitrosourea. Cl 4 cells, like the Mer- cells, did not repair O6-methylguanine (O6MeG). The results suggest that the two characteristics which are usually coupled with the Mer- phenotype--lack of O6MeG repair and hypersensitivity to MNNG--can be separated.