PMID- 8681962
OWN - NLM
STAT- MEDLINE
DCOM- 19960822
LR  - 20231213
IS  - 0014-2956 (Print)
IS  - 0014-2956 (Linking)
VI  - 238
IP  - 2
DP  - 1996 Jun 1
TI  - The identification of 11 beta-hydroxysteroid dehydrogenase as carbonyl reductase 
      of the tobacco-specific nitrosamine 
      4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.
PG  - 484-9
AB  - The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone 
      (NC), which is generated by nitrosation of nicotine, requires enzymatic 
      activation by cytochrome-P450-mediated alpha-carbon hydroxylation to yield 
      particularly powerful carcinogenic alkylating intermediates. Pyridine-N-oxidation 
      and carbonyl reduction are detoxification pathways, the latter by providing the 
      functional hydroxy moiety necessary for glucuronosylation and final excretion of 
      NC. For more than a decade, the enzyme responsible for NC carbonyl reduction has 
      awaited characterization. In the present study, we demonstrate that the NC 
      carbonyl reductase is identical to 11 beta-hydroxysteroid dehydrogenase (11 
      beta-HSD), the physiological function of which is the oxidoreduction of 
      glucocorticoids. We conclude that the expression of 11 beta-HSD (together with 
      glucuronosyl transferase) may have profound influence on the carcinogenic potency 
      of NC and that many compounds of endogenous and exogenous origin, which are known 
      to be substrates or inhibitors of 11 beta-HSD, may modulate NNK-induced 
      carcinogenicity by competing for the same enzyme. In light of the known species 
      and tissue differences in the expression of 11 beta-HSD isozymes, important 
      aspects of NNK-induced tumorigenesis, such as metabolic activation versus 
      inactivation or organospecificity, can now be re-evaluated.
FAU - Maser, E
AU  - Maser E
AD  - Department of Pharmacology and Toxicology, School of Medicine, University of 
      Marburg, Germany.
FAU - Richter, E
AU  - Richter E
FAU - Friebertshauser, J
AU  - Friebertshauser J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Biochem
JT  - European journal of biochemistry
JID - 0107600
RN  - 0 (Antibodies)
RN  - 0 (Carcinogens)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nitrosamines)
RN  - 7M56WXK8NC (4-(methylnitrosoamino)-4-(3-pyridyl)-1-butanol)
RN  - 7S395EDO61 (4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone)
RN  - EC 1.- (Oxidoreductases)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases)
RN  - FO4V44A3G3 (11-dehydrocorticosterone)
RN  - P540XA09DR (Glycyrrhetinic Acid)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenases
MH  - Animals
MH  - Antibodies/immunology
MH  - Carcinogens/*metabolism
MH  - Corticosterone/analogs & derivatives/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Glycyrrhetinic Acid/pharmacology
MH  - Hydroxysteroid Dehydrogenases/antagonists & inhibitors/*metabolism
MH  - Kinetics
MH  - Liver/*metabolism
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Molecular Structure
MH  - Nitrosamines/*metabolism
MH  - Oxidation-Reduction
MH  - Oxidoreductases/metabolism
MH  - *Plants, Toxic
MH  - Nicotiana/*chemistry
EDAT- 1996/06/01 00:00
MHDA- 1996/06/01 00:01
CRDT- 1996/06/01 00:00
PHST- 1996/06/01 00:00 [pubmed]
PHST- 1996/06/01 00:01 [medline]
PHST- 1996/06/01 00:00 [entrez]
AID - 10.1111/j.1432-1033.1996.0484z.x [doi]
PST - ppublish
SO  - Eur J Biochem. 1996 Jun 1;238(2):484-9. doi: 10.1111/j.1432-1033.1996.0484z.x.