RGD Reference Report - 4-Aminobiphenyl downregulation of NAT2 acetylator genotype-dependent N- and O-acetylation of aromatic and heterocyclic amine carcinogens in primary mammary epithelial cell cultures from rapid and slow acetylator rats. - Rat Genome Database

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4-Aminobiphenyl downregulation of NAT2 acetylator genotype-dependent N- and O-acetylation of aromatic and heterocyclic amine carcinogens in primary mammary epithelial cell cultures from rapid and slow acetylator rats.

Authors: Jefferson, FA  Xiao, GH  Hein, DW 
Citation: Jefferson FA, etal., Toxicol Sci. 2009 Jan;107(1):293-7. Epub 2008 Oct 8.
RGD ID: 5131545
Pubmed: PMID:18842621   (View Abstract at PubMed)
PMCID: PMC2605175   (View Article at PubMed Central)
DOI: DOI:10.1093/toxsci/kfn216   (Journal Full-text)

Aromatic and heterocyclic amine carcinogens present in the diet and in cigarette smoke induce breast tumors in rats. N-acetyltransferase 1 (NAT1) and N-acetyltransferase 2 (NAT2) enzymes have important roles in their metabolic activation and deactivation. Human epidemiological studies suggest that genetic polymorphisms in NAT1 and/or NAT2 modify breast cancer risk in women exposed to these carcinogens. p-Aminobenzoic acid (selective for rat NAT2) and sulfamethazine (SMZ; selective for rat NAT1) N-acetyltransferase catalytic activities were both expressed in primary cultures of rat mammary epithelial cells. PABA, 2-aminofluorene, and 4-aminobiphenyl N-acetyltransferase and N-hydroxy-2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine and N-hydroxy-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline O-acetyltransferase activities were two- to threefold higher in mammary epithelial cell cultures from rapid than slow acetylator rats. In contrast, SMZ (a rat NAT1-selective substrate) N-acetyltransferase activity did not differ between rapid and slow acetylators. Rat mammary cells cultured in the medium supplemented 24 h with 10muM ABP showed downregulation in the N-and O-acetylation of all substrates tested except for the NAT1-selective substrate SMZ. This downregulation was comparable in rapid and slow NAT2 acetylators. These studies clearly show NAT2 acetylator genotype-dependent N- and O-acetylation of aromatic and heterocyclic amine carcinogens in rat mammary epithelial cell cultures to be subject to downregulation by the arylamine carcinogen ABP.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to xenobiotic stimulus  IEP 5131545 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nat2  (N-acetyltransferase 2)


Additional Information