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dc.contributor.authorHobin, D A
dc.contributor.authorFairbairn, Leslie J
dc.date.accessioned2009-09-24T09:26:46Z
dc.date.available2009-09-24T09:26:46Z
dc.date.issued2002-02
dc.identifier.citationGenetic chemoprotection with mutant O6-alkylguanine-DNA-alkyltransferases. 2002, 2 (1):1-8notCurr Gene Theren
dc.identifier.issn1566-5232
dc.identifier.pmid12108970
dc.identifier.doi10.2174/1566523023348255
dc.identifier.urihttp://hdl.handle.net/10541/82440
dc.description.abstractOne of the main barriers to more efficacious use of modern chemotherapeutic agents, is the collateral toxicity exhibited in normal, highly proliferative tissues, primarily the haemopoietic, gastrointestinal and pulmonary tissues. Drug resistance of tumours to these drugs compounds this problem. This review discusses the role of O6-alkylguanine-DNA alkyltransferase (ATase) in conferring protection against O6-alkylating agents in normal tissue, focusing mainly on the haemopoietic compartment. The development of mutant forms of ATase, which are resistant to the effects of soluble analogues of O6-alkylation such as O6-benzylguanine, is examined and the gene therapy approach of combining these two strategies to confer chemoprotection to vulnerable tissues whilst sensitising malignant tissue is reviewed.
dc.language.isoenen
dc.subject.meshAnimals
dc.subject.meshBlood Platelets
dc.subject.meshGene Transfer Techniques
dc.subject.meshHumans
dc.subject.meshLeukocytes
dc.subject.meshMutation
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase
dc.subject.meshTime Factors
dc.titleGenetic chemoprotection with mutant O6-alkylguanine-DNA-alkyltransferases.en
dc.typeArticleen
dc.contributor.departmentCRC Gene Therapy Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester, M20 4BX, UK.en
dc.identifier.journalCurrent Gene Therapyen
html.description.abstractOne of the main barriers to more efficacious use of modern chemotherapeutic agents, is the collateral toxicity exhibited in normal, highly proliferative tissues, primarily the haemopoietic, gastrointestinal and pulmonary tissues. Drug resistance of tumours to these drugs compounds this problem. This review discusses the role of O6-alkylguanine-DNA alkyltransferase (ATase) in conferring protection against O6-alkylating agents in normal tissue, focusing mainly on the haemopoietic compartment. The development of mutant forms of ATase, which are resistant to the effects of soluble analogues of O6-alkylation such as O6-benzylguanine, is examined and the gene therapy approach of combining these two strategies to confer chemoprotection to vulnerable tissues whilst sensitising malignant tissue is reviewed.


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