Sister-chromatid exchanges (SCEs), cell survival and mutation in HeLa s3 cells with different sensitivity to alkylating agents; evidence that SCE induction and cell survival or mutation induction are dissociable.
We previously isolated N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-resistant cells, MR from HeLa S3 Mer- cells. In the present study, we have isolated 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU)-resistant cells, ACr. The MR cells had only a little O6-methylguanine-DNA methyltransferase (MT) activity, while the ACr cells had increased MT activity and also became resistant to the cytotoxic effect of MNNG. We compared the induction of sister-chromatid exchanges (SCEs), cell survival and mutation in these HeLa S3 cells with different sensitivity to MNNG. The ACr cells were much more resistant than the parental HeLa S3 Mer- cells to cytotoxicity, mutagenicity and SCE induction by MNNG, showing a positive correlation between SCE induction and cell killing or mutation. In contrast, this positive relationship was not observed between HeLa S3 Mer- and MR cells. These results suggest that O6-methylguanine (O6-MeG) is involved in the induction of the biological effects of MNNG such as cytotoxicity, mutagenicity and SCEs, and also indicate that SCE induction does not always correlate with cell killing and mutation.
Ishida
R
R
Laboratory of Biochemistry, Aichi Cancer Center Research Institute, Nagoya, Japan.
Utsumi
K R
KR
Takahashi
T
T
D000477:Alkylating Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects*; D006367:HeLa Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008130:Lomustine / Q000494:pharmacology; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D009154:Mutation; D015376:Nimustine / Q000494:pharmacology; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000477:Alkylating Agents; D015376:Nimustine; D008769:Methylnitronitrosoguanidine; D008130:Lomustine