High capacity of human skin for N-acetylation of arylamines.
Human skin showed high activity of cytosolic N-acetylation for two typical arylamine substrates, p-aminobenzoic acid (PABA) and 2-aminofluorene (AF). Their specific activities (per milligram protein basis) were comparable with those of hamster skin, which is known to have high acetylating capacities for several arylamines. In hamster skin, two other types of acetylation, N-hydroxy-4-acetylaminobiphenyl-dependent N-acetylation of AF (N,N'-acetyltransfer) and acetyl CoA-dependent O-acetylation of 2-hydroxyamino-6-methyl-pyrido[1,2-a:3',2'-d]imidazole (O-acetylation) also occurred, but no appreciable activity was observed in human skin for these two reactions. These results suggest that arylamines including prohaptens and carcinogens may be modified metabolically through N-acetylation at the first contact site, human skin. In addition, a good correlation was observed for N-acetylations of PABA and AF in human skin, implying that these N-acetylations may be catalyzed by the same or a closely related enzyme in human skin.
Kawakubo
Y
Y
Department of Dermatology, School of Medicine, Keio University, Tokyo, Japan.
Yamazoe
Y
Y
Kato
R
R
Nishikawa
T
T
D010129:4-Aminobenzoic Acid / Q000493:pharmacokinetics*; D000107:Acetylation; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism; D006224:Cricetinae; D005449:Fluorenes / Q000493:pharmacokinetics*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D012867:Skin / Q000378:metabolism*
D005449:Fluorenes; C012177:2-aminofluorene; D001191:Arylamine N-Acetyltransferase; D010129:4-Aminobenzoic Acid