The Role of O6-Methylguanine in Human Cell Killing, Sister Chromatid Exchange Induction and Mutagenesis: A Review
Open Access
- 1 January 1987
- journal article
- review article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 1987 (Supplement), 333-353
- https://doi.org/10.1242/jcs.1984.supplement_6.22
Abstract
O 6-methylguanine ( O 6mG) produced in DNA by such SN1 methylating agents as N -methyl- N -nitrososurea and N -methyl- N ′-nitro- N -nitrosoguanidine (MNNG) has been suggested by some to be the lesion that leads to certain biological endpoints in mammalian cells: cell killing, sister chromatid exchange (SCE) production, mutagenesis and cellular transformation. Other evidence is interpreted as inconsistent with this point of view. The finding of Karran & Williams (1985) that O 6mG delivered to cells in culture resulted in the depletion of the activity of the protein responsible for repair of O 6mG in DNA ( O 6mG-DNA methyltransferase, O 6MT) provided a tool for the assessment of the role of O 6mG in producing biological endpoints. In this paper we review much of the literature on human cells pertinent to this question. In addition we present our survival data obtained using the depletion technique of Karran & Williams as well as data supporting a model invoking a mismatch and excision response to O 6mG proposed by Sklar & Strauss (1980). Although data linking O 6mG to causation are inconclusive, it is premature to conclude that O 6mG is not a lesion lethal to certain cultured cells.Keywords
This publication has 44 references indexed in Scilit:
- Methylation-induced blocks to in vitro DNA replicationMutation Research, 1985
- Methylating agents: their target amino acids in nuclear proteinsCarcinogenesis: Integrative Cancer Research, 1985
- Human O6-alkylguanine-DNA alkyltransferase fails to repair O4-methylthymine and methyl phosphotriesters in DNA as efficiently as does the alkyltransferase from Escherichia coliCarcinogenesis: Integrative Cancer Research, 1985
- The cytotoxic and mutagenic effects of alkylating agents on human lymphoid cells are caused by different DNA lesionsCarcinogenesis: Integrative Cancer Research, 1985
- Depletion of O6-methylguanine-DNA-methyltransferase in human fibroblasts increases the mutagenic response to N-methyl-N'-nitro-N-nitrosoguanidineCarcinogenesis: Integrative Cancer Research, 1985
- Correlation between O6-methylguanine-DNA-methyltransferase activity and resistance of human cells to the cytotoxic and mutagenic effect of N-methyl-N′-nitro-N-nitrosoguanidineCarcinogenesis: Integrative Cancer Research, 1984
- The adaptive response to alkylating agents the removal of O6-methylguanine from DNA is not dependent on DNA polymerase-1Mutation Research Letters, 1982
- Mismatch correction at O6-methylguanine residues in E. coli DNANature, 1982
- The removal of alkylation products from the DNA of Escherichia coli cells treated with the carcinogens N-ethyl-N-nitrosourea and N-methyl-N-nitrosourea: influence of growth conditions and DNA repair defectsCarcinogenesis: Integrative Cancer Research, 1980
- Selectivity of the excision of alkylation products in a xeroderma pigmentosum-derived lymphoblastoid lineMutation Research, 1979