Suppression of human DNA alkylation-repair defects by Escherichia coli DNA-repair genes
L Samson,B Derfler,E A Waldstein +2 more
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The subcloned ada-alkB operon protects Escherichia coli against the effects of many alkylating agents and is introduced into Mer- HeLa S3 cells, which are extremely sensitive to killing and induction of sister chromatid exchange by alkyLating agents.Abstract:
The ada-alkB operon protects Escherichia coli against the effects of many alkylating agents. We have subcloned it into the pSV2 mammalian expression vector to yield pSV2ada-alkB, and this plasmid has been introduced into Mer- HeLa S3 cells, which are extremely sensitive to killing and induction of sister chromatid exchange by alkylating agents. One transformant (the S3-9 cell line) has several integrated copies of pSV2ada-alkB and was found to express a very high level of the ada gene product, the 39-kDa O6-methylguanine-DNA methyltransferase. S3-9 cells were found to have become resistant to killing and induction of sister chromatid exchange by two alkylating agents, N-methyl-N'-nitro-N-nitrosoguanidine and N,N'-bis(2-chloroethyl)-N-nitro-sourea. This shows that bacterial DNA alkylation-repair genes are able to suppress the alkylation-repair defects in human Mer- cells.read more
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Journal Article
Mammalian O6-alkylguanine-DNA alkyltransferase: regulation and importance in response to alkylating carcinogenic and therapeutic agents.
TL;DR: Alkylating agents and compounds converted metabolically to alkylates agents form an important class of carcinogens and mutagens that includes a number of environmentally important /V-nitrosocompounds.
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Depletion of mammalian O6-alkylguanine-DNA alkyltransferase activity by O6-benzylguanine provides a means to evaluate the role of this protein in protection against carcinogenic and therapeutic alkylating agents
TL;DR: Results indicate that depletion of the alkyltransferase by O6-benzylguanine may be used to investigate the role of the DNA repair protein in carcinogenesis and mutagenesis and that this treatment may be valuable to increase the chemotherapeutic effectiveness of chloroethylating agents.
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DNA alkylation by the haloethylnitrosoureas: nature of modifications produced and their enzymatic repair or removal.
TL;DR: Following the observation that N-methyl-N'nitro-N-nitrosoguanidine had antitumor activity against L1210 cells, related compounds were synthesized and tested as antitumors at the Southern Research Institute and led to the development of the haloethylnitrosoureas.
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Chromosomal instability, reproductive cell death and apoptosis induced by O6-methylguanine in Mex-, Mex+ and methylation-tolerant mismatch repair compromised cells: facts and models.
TL;DR: O6-MeG is a potent clastogenic DNA damage that needs two DNA replication cycles in order to be transformed with high efficiency into aberrations and the same holds true for sister chromatid exchanges (SCEs).
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Mechanisms of carcinogenicity/chemotherapy by O6-methylguanine.
TL;DR: There is increasing evidence that point mutations are not the only mechanism involved in malignant transformation by alkylating agents, and an understanding of the processing of this lesion has allowed strategies to be developed that should increase the effectiveness of such agents.
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Transcription and translation : a Practical Approach
B.D. Hames,Stephen J. Higgins +1 more
TL;DR: This work aims to demonstrate the efforts towards in-vitro transcription-translation-translation co-operation in prokaryotic cell-free systems and demonstrates the ability of these systems to co-operate with each other on the basis of individual cell types.