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Titolo:
ROLE OF ACETYLTRANSFERASES IN THE METABOLISM AND CARCINOGENICITY OF AROMATIC-AMINES
Autore:
KING CM; LAND SJ; JONES RF; DEBIECRYCHTER M; LEE MS; WANG CY;
Indirizzi:
KARMANOS CANC INST,CARCINOGENESIS PROGRAM,110 E WARREN AVE DETROIT MI48201 KARMANOS CANC INST,CARCINOGENESIS PROGRAM DETROIT MI 48201 WAYNE STATE UNIV DETROIT MI 48201
Titolo Testata:
Mutation research
fascicolo: 1-2, volume: 376, anno: 1997,
pagine: 123 - 128
SICI:
0027-5107(1997)376:1-2<123:ROAITM>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT MAMMARY-GLAND; ARYLAMINE N-ACETYLTRANSFERASE; ARYLHYDROXAMIC ACID N,O-ACYLTRANSFERASE; HYDROXYARYLAMINE-O-ACETYLTRANSFERASE; DNA ADDUCTS; URINARY-BLADDER; ACTIVATION; LIVER; PURIFICATION; TRANSACETYLATION;
Keywords:
ACETYLTRANSFERASE; AROMATIC AMINE; ARYLALKYLAMINE; GENOTOXICITY; HISTOLOGICAL LOCALIZATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
22
Recensione:
Indirizzi per estratti:
Citazione:
C.M. King et al., "ROLE OF ACETYLTRANSFERASES IN THE METABOLISM AND CARCINOGENICITY OF AROMATIC-AMINES", Mutation research, 376(1-2), 1997, pp. 123-128

Abstract

The genotoxicity of N-substituted aryl compounds is dependent on their conversion to reactive metabolites, frequently through the production of reactive N-acetoxyarylamines. This activation is accomplished by acetyltransferases that are widely distributed. In the rat, the production of N-acetoxyarylamines has been most clearly related to the induction of tumors in the mammary gland, but this pathway also appears to be an important factor in the production of tumors in the liver, Zymbal gland and gastrointestinal tract. Expression of rat acetyltransferases responsible for acetylation of the nitrogen and the oxygen of arylamine derivatives (i.e., acetyltransferases 1 and 2) in bacterial cellshas now permitted experiments which demonstrate that these enzymes exhibit good affinities for and N-acetylation of the endogenous arylalkylamines derived from tryptophan, i.e., tryptamine, 5-hydroxytryptamine(serotonin) and 5-methoxytryptamine, the immediate metabolic precursor of melatonin. Evidence that these reactions are likely to reflect real biological potentials is bolstered by histological localization of acetyltransferase mRNAs with synthetic antisense oligodeoxynucleotide probes. The results of these studies in rat indicate that the expression of acetyltransferase in tissues of the central nervous, gastrointestinal, urinary and reproductive systems is highly regulated, as it is in other organs commonly associated with aromatic amine carcinogenicity, Similar experimental approaches have been successful with human liver, mammary gland, kidney and bladder preparations. These observationsgive evidence that genotoxic N-acetoxyarylamines are produced by acetyltransferases that can metabolize, and possibly modulate, the hormonal and neurotransmitter effects of endogenous arylalkylamines. These relationships may help explain the occasional induction of tumors in organs not usually considered as targets of aromatic amines, as well as raise the possibility that the production of N-oxidized endogenous substrates may represent a mechanism for tumor induction in the absence ofexogenous carcinogens.

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Documento generato il 28/09/20 alle ore 12:04:03