2.50
Hdl Handle:
http://hdl.handle.net/10541/84373
Title:
Mechanisms of carcinogenicity/chemotherapy by O6-methylguanine.
Authors:
Margison, Geoffrey P; Santibanez-Koref, Mauro F; Povey, Andrew C
Abstract:
Alkylating agents are a structurally diverse group of compounds that cause a wide range of biological effects, including cell death, mutation and cancer. DNA damaged by these agents contains widely different amounts of 12 alkylated purines/pyrimidines and two phosphotriester isomers. The biological effects appear to be mediated predominantly by attack at the O(6) position of guanine. DNA extracted from various normal human tissues contains detectable levels of O(6)-alkylguanine, the source of which has not been defined. Given that, following DNA replication, this lesion cannot only generate point mutations but can also initiate mismatch repair-mediated DNA recombination and cell death, it seems worthwhile to consider the possible contribution of these events and cell killing to the aetiology of human cancer. There is increasing evidence that point mutations are not the only mechanism involved in malignant transformation by alkylating agents. Some cancer chemotherapeutic agents exploit the cytotoxic effects of O(6)-alkylguanine and an understanding of the processing of this lesion has allowed strategies to be developed that should increase the effectiveness of such agents.
Affiliation:
Cancer Research UK Carcinogenesis Group, Paterson Institute for Cancer Research, Manchester M20 4BX, UK. gmargison@picr.man.ac.uk
Citation:
Mechanisms of carcinogenicity/chemotherapy by O6-methylguanine. 2002, 17 (6):483-7 Mutagenesis
Journal:
Mutagenesis
Issue Date:
Nov-2002
URI:
http://hdl.handle.net/10541/84373
DOI:
10.1093/mutage/17.6.483
PubMed ID:
12435845
Type:
Article
Language:
en
ISSN:
0267-8357
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorMargison, Geoffrey Pen
dc.contributor.authorSantibanez-Koref, Mauro Fen
dc.contributor.authorPovey, Andrew Cen
dc.date.accessioned2009-10-16T15:07:52Z-
dc.date.available2009-10-16T15:07:52Z-
dc.date.issued2002-11-
dc.identifier.citationMechanisms of carcinogenicity/chemotherapy by O6-methylguanine. 2002, 17 (6):483-7 Mutagenesisen
dc.identifier.issn0267-8357-
dc.identifier.pmid12435845-
dc.identifier.doi10.1093/mutage/17.6.483-
dc.identifier.urihttp://hdl.handle.net/10541/84373-
dc.description.abstractAlkylating agents are a structurally diverse group of compounds that cause a wide range of biological effects, including cell death, mutation and cancer. DNA damaged by these agents contains widely different amounts of 12 alkylated purines/pyrimidines and two phosphotriester isomers. The biological effects appear to be mediated predominantly by attack at the O(6) position of guanine. DNA extracted from various normal human tissues contains detectable levels of O(6)-alkylguanine, the source of which has not been defined. Given that, following DNA replication, this lesion cannot only generate point mutations but can also initiate mismatch repair-mediated DNA recombination and cell death, it seems worthwhile to consider the possible contribution of these events and cell killing to the aetiology of human cancer. There is increasing evidence that point mutations are not the only mechanism involved in malignant transformation by alkylating agents. Some cancer chemotherapeutic agents exploit the cytotoxic effects of O(6)-alkylguanine and an understanding of the processing of this lesion has allowed strategies to be developed that should increase the effectiveness of such agents.en
dc.language.isoenen
dc.subjectCanceren
dc.subject.meshAlkylating Agents-
dc.subject.meshAnimals-
dc.subject.meshDNA-
dc.subject.meshDNA Adducts-
dc.subject.meshDNA Damage-
dc.subject.meshDNA Methylation-
dc.subject.meshGuanine-
dc.subject.meshHumans-
dc.subject.meshNeoplasms-
dc.subject.meshPoint Mutation-
dc.subject.meshRecombination, Genetic-
dc.titleMechanisms of carcinogenicity/chemotherapy by O6-methylguanine.en
dc.typeArticleen
dc.contributor.departmentCancer Research UK Carcinogenesis Group, Paterson Institute for Cancer Research, Manchester M20 4BX, UK. gmargison@picr.man.ac.uken
dc.identifier.journalMutagenesisen

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