PMID- 3568192
OWN - NLM
STAT- MEDLINE
DCOM- 19870602
LR  - 20190824
IS  - 0009-2797 (Print)
IS  - 0009-2797 (Linking)
VI  - 61
IP  - 3
DP  - 1987 Mar
TI  - An investigation of the metabolism of N-nitroso-N-methylaniline by phenobarbital- 
      and pyrazole-induced Sprague-Dawley rat liver and esophagus derived S-9.
PG  - 215-28
AB  - The metabolism and mutagenicity of the esophageal carcinogen 
      N-nitroso-N-methylaniline (NMA) was studied using hepatic and esophageal 9000 X g 
      supernatant (S-9) preparations from Sprague-Dawley rats induced with pyrazole and 
      phenobarbital. Only pyrazole-induced hepatic S-9 was able to dose-dependently 
      activate NMA to a mutagen in the Ames assay and specifically in Salmonella 
      typhimurium TA1537. NMA in the presence of phenobarbital-induced S-9 gave a very 
      weak non-dose dependent mutagenic response. Metabolism of NMA by the two induced 
      hepatic and esophageal S-9 fractions yielded aniline and N-methylaniline (MA). 
      Phenobarbital-induced S-9 from both tissues also afforded phenol, while none was 
      found with the pyrazole-induced preparations. Phenol formation presumably arose 
      from the direct oxidative demethylation of NMA via a benzenediazonium ion (BDI) 
      intermediate. The results indicate that an important metabolic pathway for NMA, 
      with both inducing agents, entails an initial denitrosation to yield MA, which in 
      turn rapidly undergoes oxidative demethylation to aniline. The conversion of NMA 
      to phenol also suggests that direct demethylation of NMA in the 
      phenobarbital-induced system is an important metabolic pathway.
FAU - Gold, B
AU  - Gold B
FAU - Farber, J
AU  - Farber J
FAU - Rogan, E
AU  - Rogan E
LA  - eng
GR  - CA36727/CA/NCI NIH HHS/United States
GR  - R01 CA38976/CA/NCI NIH HHS/United States
GR  - SO7 RR05391/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Ireland
TA  - Chem Biol Interact
JT  - Chemico-biological interactions
JID - 0227276
RN  - 0 (Mutagens)
RN  - 0 (Nitrosamines)
RN  - 0 (Pyrazoles)
RN  - 3QD5KJZ7ZJ (pyrazole)
RN  - 9SM68I29WQ (N-methyl-N-nitrosoaniline)
RN  - YQE403BP4D (Phenobarbital)
SB  - IM
MH  - Animals
MH  - Biotransformation
MH  - Electrochemistry
MH  - Enzyme Induction/drug effects
MH  - Esophagus/*metabolism
MH  - In Vitro Techniques
MH  - Liver/*metabolism
MH  - Male
MH  - Mutagenicity Tests
MH  - Mutagens/*metabolism
MH  - Nitrosamines/*metabolism
MH  - Oxidation-Reduction
MH  - Phenobarbital/pharmacology
MH  - Pyrazoles/pharmacology
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Subcellular Fractions/metabolism
EDAT- 1987/03/01 00:00
MHDA- 1987/03/01 00:01
CRDT- 1987/03/01 00:00
PHST- 1987/03/01 00:00 [pubmed]
PHST- 1987/03/01 00:01 [medline]
PHST- 1987/03/01 00:00 [entrez]
AID - 0009-2797(87)90002-0 [pii]
AID - 10.1016/0009-2797(87)90002-0 [doi]
PST - ppublish
SO  - Chem Biol Interact. 1987 Mar;61(3):215-28. doi: 10.1016/0009-2797(87)90002-0.