PMID- 7748887
OWN - NLM
STAT- MEDLINE
DCOM- 19950621
LR  - 20190610
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1229
IP  - 3
DP  - 1995 May 10
TI  - A metabolite of carcinogenic 2-acetylaminofluorene, 2-nitrosofluorene, induces 
      redox cycling in mitochondria.
PG  - 363-72
AB  - The present study was designed to confirm the recent proposal that 
      2-nitrosofluorene (2-NOF) as well as N-hydroxy-2-aminofluorene (N-OH-AF) induce a 
      redox-cycle in rat liver mitochondria as part of the chronic toxic effects of the 
      carcinogen 2-acetylaminofluorene (2-AAF). The formation of O2.- was demonstrated 
      in submitochondrial particles by the formation of adrenochrome with NADH and 
      succinate as respiratory substrates. 2-NOF was as effective as paraquat, a known 
      redox-cycler, the lowest effective concentration being 0.4 nmol 2-NOF/mg protein. 
      Experiments with isolated mitochondria showed that 2-NOF, in contrast to N-OH-AF, 
      induces cyanide-resistant O2 consumption only in the presence of respiratory 
      substrates, indicating that the reduction, but not the reoxidation, depends on a 
      continuous flow of electrons through the respiratory chain of the mitochondrial 
      membrane. Lipid peroxidation was estimated by the formation of 
      thiobarbituric-acid-reactive substances. In comparison to the well-known 
      prooxidant tert-butylhydroperoxide, 2-NOF was not significantly active. The 
      results support the notion that 2-NOF induces oxidative stress by mitochondrial 
      redox-cycling in vivo. Effects other than lipid peroxidation seem to be important 
      for the chronic toxicity of 2-AAF.
FAU - Klohn, P C
AU  - Klohn PC
AD  - Institute of Pharmacology and Toxicology, University of Wurzburg, Germany.
FAU - Massalha, H
AU  - Massalha H
FAU - Neumann, H G
AU  - Neumann HG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Albumins)
RN  - 0 (Fluorenes)
RN  - 0 (Nitroso Compounds)
RN  - 11062-77-4 (Superoxides)
RN  - 34E9V9B29K (2-nitrosofluorene)
RN  - 61M94X4V24 (N-hydroxy-2-aminofluorene)
RN  - 9M98QLJ2DL (2-Acetylaminofluorene)
SB  - IM
MH  - 2-Acetylaminofluorene/*metabolism/toxicity
MH  - Albumins/pharmacology
MH  - Animals
MH  - Fluorenes/metabolism
MH  - Male
MH  - Mitochondria, Liver/*metabolism
MH  - Nitroso Compounds/*metabolism/pharmacology
MH  - Oxidation-Reduction
MH  - Oxygen Consumption
MH  - Rats
MH  - Rats, Wistar
MH  - Substrate Cycling/drug effects
MH  - Superoxides/metabolism
EDAT- 1995/05/10 00:00
MHDA- 1995/05/10 00:01
CRDT- 1995/05/10 00:00
PHST- 1995/05/10 00:00 [pubmed]
PHST- 1995/05/10 00:01 [medline]
PHST- 1995/05/10 00:00 [entrez]
AID - 0005-2728(95)00019-F [pii]
AID - 10.1016/0005-2728(95)00019-f [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 1995 May 10;1229(3):363-72. doi: 
      10.1016/0005-2728(95)00019-f.