A simple identification of novel carbonyl reducing enzymes in the metabolism of the tobacco specific carcinogen NNK

Tobacco smoking is the most widely known cause of human cancer-related death worldwide. NNK is one of the proved human carcinogens contributing to the development of several types of cancer. The carcinogenic effect of NNK depends on the metabolic pathway. Reduction of NNK by carbonyl reducing enzyme...

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Bibliographic Details
Published inDrug metabolism letters Vol. 6; no. 3; p. 174
Main Authors Skarydova, Lucie, Zverinova, Michaela, Stambergova, Hana, Wsol, Vladimir
Format Journal Article
LanguageEnglish
Published United Arab Emirates 01.09.2012
Subjects
Alcohol Oxidoreductases - metabolism
Carcinogens - metabolism
Chromatography, High Pressure Liquid - methods
Humans
Microsomes, Liver - metabolism
Nitrosamines - analysis
Nitrosamines - metabolism
Pyridines - analysis
Smoking - adverse effects
Smoking - metabolism
Stereoisomerism
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Summary:Tobacco smoking is the most widely known cause of human cancer-related death worldwide. NNK is one of the proved human carcinogens contributing to the development of several types of cancer. The carcinogenic effect of NNK depends on the metabolic pathway. Reduction of NNK by carbonyl reducing enzymes leads to the formation of NNAL. This pathway is generally regarded as detoxification pathway although the conditions and circumstances are quite complicated - the process depends on a formed enantiomer of NNAL. In this study a novel method for the determination of the metabolite NNAL was developed. This makes it possible to findand characterize carbonyl reducing enzymes that are involved in NNK metabolism. This simple HPLC method uses conventional HPLC instrumentation and is designed mainly for biochemical laboratories. A new microsomal carbonyl reducing enzyme participating in the metabolism of NNK in vitro has been described. Its activity was compared with other carbonyl reducing enzymes taking part in the biotransformation of NNK.
ISSN:1874-0758