AN ETHOXYQUIN-INDUCIBLE ALDEHYDE REDUCTASE FROM RAT-LIVER THAT METABOLIZES AFLATOXIN-B(1) DEFINES A SUBFAMILY OF ALDO-KETO REDUCTASES

Protection of liver against the toxic and carcinogenic effects of afla toxin B1 (AFB1) can be achieved through the induction of detoxificatio n enzymes by chemoprotectors such as the phenolic antioxidant ethoxyqu in. We have cloned and sequenced a cDNA encoding an aldehyde reductase (AFB1-AR), which is expressed in rat liver in response to dietary eth oxyquin. Expression of the cDNA in Escherichia coli and purification o f the recombinant enzyme reveals that the protein exhibits aldehyde re ductase activity and is capable of converting the protein-binding dial dehyde form of AFB1-dihydrodiol to the nonbinding dialcohol metabolite . We show that the mRNA encoding this enzyme is markedly elevated in t he liver of rats fed an ethoxyquin-containing diet, correlating with a cquisition of resistance to AFB1. AFB1-AR represents the only carcinog en-metabolizing aldehyde reductase identified to date that is induced by a chemoprotector. Alignment of the amino acid sequence of AFB1-AR w ith other known and putative aldehyde reductases shows that it defines a subfamily within the aldo-keto reductase superfamily.