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Current Gene Therapy

Editor-in-Chief

ISSN (Print): 1566-5232
ISSN (Online): 1875-5631

Genetic Chemoprotection with Mutant O6-Alkylguanine-DNA-Alkyltransferases

Author(s): D. A. Hobin and L. J. Fairbairn

Volume 2, Issue 1, 2002

Page: [1 - 8] Pages: 8

DOI: 10.2174/1566523023348255

Price: $65

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

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