Genetic Chemoprotection with Mutant O6-Alkylguanine-DNA-Alkyltransferases

Authors: Hobin D.A.; Fairbairn L.J.

Source: Current Gene Therapy, Volume 2, Number 1, February 2002 , pp. 1-8(8)

Publisher: Bentham Science Publishers

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Abstract:

One 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.

Keywords: Genetic Chemoprotection; Alkylguanine-DNA-Alkyltrans-ferases; haemopoietic compartment; collateral toxicity; cytosine arabinoside

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1566523023348255

Publication date: 2002-02-01