PMID- 3890753
OWN - NLM
STAT- MEDLINE
DCOM- 19850624
LR  - 20190629
IS  - 0003-9861 (Print)
IS  - 0003-9861 (Linking)
VI  - 239
IP  - 1
DP  - 1985 May 15
TI  - Metabolic activation of mutagenic N-hydroxyarylamines by O-acetyltransferase in 
      Salmonella typhimurium TA98.
PG  - 286-95
AB  - A new enzymatic activation of mutagenic N-hydroxyarylamines is described. An 
      acetyl-CoA dependent enzyme that can activate 
      2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-OH-Glu-P-1) to a 
      reactive species capable of binding to nucleic acid was found in a cell-free 
      extract of Salmonella typhimurium TA98 but not in that of TA98/1,8-DNP6, which 
      shows low sensitivity to the mutagenic activity of N-OH-Glu-P-1. The enzyme was 
      partially purified by streptomycin treatment, ammonium sulfate precipitation, 
      DEAE-cellulose chromatography, and gel filtration chromatography of Sephadex 
      G-150. Its molecular weight was estimated to be approximately 48,000. The 
      directly mutagenic N-hydroxyarylamines, such as N-OH-Glu-P-1, 
      3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole (N-OH-Trp-P-2), and 
      N-hydroxy-2-aminofluorene (N-OH-AF), were transformed to reactive derivatives by 
      partially purified enzyme in the presence of acetyl-CoA. The Km value for 
      acetyl-CoA was calculated to be 3.3 microM. No acetyl residue, however, was 
      incorporated into nucleic acid adducts. The enzymatic product of N-OH-Glu-P-1 
      bound most efficiently to polyguanylic acid among four polynucleotides. The 
      enzyme did not show the N,O-acetyltransfer activity of 
      N-hydroxyacetylaminofluorene (N-OH-AAF). These results indicate that the 
      enzymatic product of N-hydroxyarylamine is N-acetoxyarylamine, and that this 
      enzyme can be called acetyl-CoA:N-hydroxyarylamine O-acetyltransferase. 
      O-Acetyltransferase activity was inhibited by SH-blocking agents, several 
      phenolic compounds, such as pentachlorophenol and 1-nitro-2-naphthol, and an 
      antibiotic thiolactomycin. S. typhimurium mutation studies suggested that the 
      O-acetyltransferase functions as an enzyme activating certain N-hydroxyarylamines 
      within bacterial cells and is involved in the formation of mutants.
FAU - Saito, K
AU  - Saito K
FAU - Shinohara, A
AU  - Shinohara A
FAU - Kamataki, T
AU  - Kamataki T
FAU - Kato, R
AU  - Kato R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arch Biochem Biophys
JT  - Archives of biochemistry and biophysics
JID - 0372430
RN  - 0 (Hydroxylamines)
RN  - 0 (Mutagens)
RN  - 0 (Sulfhydryl Compounds)
RN  - EC 2.3.1.- (Acetyltransferases)
SB  - IM
MH  - Acetyltransferases/antagonists & inhibitors/*pharmacology
MH  - Binding Sites
MH  - Biotransformation
MH  - Hydroxylamines/*metabolism/pharmacology
MH  - Mutagenicity Tests
MH  - Mutagens/*metabolism
MH  - Salmonella typhimurium/*enzymology/genetics
MH  - Substrate Specificity
MH  - Sulfhydryl Compounds/metabolism
EDAT- 1985/05/15 00:00
MHDA- 1985/05/15 00:01
CRDT- 1985/05/15 00:00
PHST- 1985/05/15 00:00 [pubmed]
PHST- 1985/05/15 00:01 [medline]
PHST- 1985/05/15 00:00 [entrez]
AID - 0003-9861(85)90838-0 [pii]
AID - 10.1016/0003-9861(85)90838-0 [doi]
PST - ppublish
SO  - Arch Biochem Biophys. 1985 May 15;239(1):286-95. doi: 
      10.1016/0003-9861(85)90838-0.