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© 1993 Oxford University Press

research-article

A human cell line proficient in O6-methylguanine-DNA-methyltransferase and hypersensitive to alkylating agents

Patricia Lefebvre and Francoise Laval 1

Groupe ‘Radiochimie de l'ADN’, U247 INSERM, Institut Gustave Roussy 94805 Villejuif, France

1To whom correspondence should be addressed

The involvement of O6-methylguanine (O6-meGua) in mutagenesis is well established, while the toxic effect of these residues is still controversial. In this study, we compare the cytotoxicity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and N-methyl-N-nitrosourea (MNU) on three cell lines of different origin, which have different abilities to repair O6-meGua residues (Mer phenotype): a human hepatoma cell line (LICH cells, Mer+), a rat hepatoma cell line (H4 cells, Mer+) and a Chinese hamster cell line (CHO cells, Mer– phenotype). LICH and CHO cells show the same sensitivity to the killing effect of MNNG and MNU and are ~ 5-fold more sensitive than H4 cells. However, LICH and H4 cells share similar sensitivities to the toxic effect of 1, 3-bis(2-chloroethyl)-l-nitrosourea. O6-meGua residues are removed at the same rate from the DNA of [3H]MNU-treated LICH and H4 cells, which also do not differ in the rate of removal of N3-methyladenine residues nor in overall DNA repair synthesis. The results suggest that MNNG and MNU produce a lethal lesion that is repaired by a process that does not involve the alkyltransferase.


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