Effects of alkylating carcinogens on human tumor cells in culture

In Escherichia coli 3-methyladenine and 3-methylguanine have been identified as lethal lesions, since two types of alkylating agent-sensitive mutants were deficient in repair of either of these lesions. Similar alkylation-sensitive human cell lines exist. These are the tumor cell lines of the complex Mer- phenotype. All Mer- cells examined were hypersensitive to killing by MNNG and other alkylating agents, and failed to repair O6-methylguanine. The widely studied HeLa S3 cell line has the Mer+ phenotype, but a Mer- variant (HeLa MR) has arisen. This offers the possibility to study Mer- and Mer+ cells of otherwise similar genetic background. We are using these two variants to analyze the Mer- phenotype further. When HeLa S3 and HeLa MR were treated with a highly dose of MNNG, and the surviving population exposed to a second dose of MNNG 2-3 weeks later, HeLa S3 (Mer+) cells were equally or even slightly more sensitive to a second exposure of MNNG, whereas the surviving HeLa MR (Mer-) population was much more resistant to MNNG. 1 fig., 1 tab