MNNG-induced partial phenotypic reversion of Mer- cells

Abstract

The effect of pretreatment with N -methyl- N '-nitro- N -nitrosoguanidine (MNNG) on MINNG 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 MINNG. 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 chloroethylntrosourea. Cl 4 cells, like the Mer ⁻ cells, did not repair O⁶ -methylguanine (O 6 MeG). The results suggest that the two characteristics which are usually coupled with the Mer ⁻ phenotype - lack of O ⁶ MeG repair and hypersensitivity to MNNG - can be separated.