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CC1-USTR: Interspecies Differences in the Metabolism of Toxic Aldehydes and Ketones by the AKR7 Family of Aldo-Keto Reductases

Principal Investigator

Dr. Elizabeth Ellis
University of Strathclyde
Pharmaceutical Sciences
George Street, 204
Glasgow, G1 1XW
UK
elizabeth.ellis@strath.ac.uk
Tel: +44 141-548 2122
Fax: +44 141-553 4124

Description

Highly reactive carbonyl compounds, aldehydes and ketones – found in a diverse range of natural and synthetic compounds – can cause cancer by damaging cell proteins and DNA. To help prevent this cells contain enzymes, which can break down these chemicals. One such group of enzymes, called aldo-keto-reductases, has been shown to protect rat cells from damage by cancer-causing chemicals formed from aflatoxin B1 a toxic substance produced naturally by certain moulds. Natural compounds in the diet have been shown to increase the levels of enzymes in rat liver, meaning that rats treated in this way become resistant to chemical carcinogens. This research aims to discover whether an equivalent human enzyme can also work in this way, a fact that could explain why a diet rich in fruit and vegetables can help prevent cancer. The scientists will also compare the effectiveness of human and rodent enzymes in detoxifying aldehydes and ketones. This will help evaluate the accuracy of rodent models. 

Related Publications

R Gardner, S Kazi, EM Ellis, Detoxication of the environmental pollutant acrolein by a rat liver aldo-keto reductase, Toxicology Letters 2004,148, 65-72.

Timeline: April 2000 > March 2003

LRI funding: €322,912

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