Properties of cutaneous acetyltransferase catalyzing N- and O-acetylation of carcinogenic arylamines and N-hydroxyarylamine.
The role of skin for N- and O-acetylations of carcinogenic arylamine and N-hydroxyarylamine was studied in vitro. Unexpectedly high activities were observed in acetyl CoA-dependent N-acetylations of 2-aminofluorene (2-AF) and p-aminobenzoic acid (PABA) in skin cytosols of hamsters. The specific activity for 2-AF (4.52 nmoles/mg protein per min) was largely the same as that of rat liver cytosols. The cutaneous cytosols also catalyzed N,N-acetyltransfer reaction from N-hydroxy-4-acetylamino-biphenyl (N-OH-AABP) to 2-AF and acetyl CoA-dependent O-acetylation of 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-OH-Glu-P-1), suggesting that hamster skin cytosol has enzymes similar to hepatic acetyltransferases. In addition, remarkably high correlations were observed between the skin and liver in the activities for N-acetylations of PABA and 2-AF. In a colony of Syrian golden hamsters a clear polymorphism was detected in the cutaneous N-acetylations of PABA and 2-AF. These animals were divided into three groups according to their activities: rapid, intermediate and slow acetylators. On the other hand, the acetylating activities in the skin and liver of these three groups showed monomorphic distribution with N-OH-AABP-dependent N,N-acetyltransfer of 2-AF and acetyl CoA-dependent O-acetylation of N-OH-Glu-P-1. These results, together with the detection of N-acetylating activity in the skin of other experimental animals and humans, suggest that skin may play an important role in the metabolism of aromatic amines and that the cutaneous acetylation in hamsters may be under the common genetic control which regulates the individual difference in the hepatic activities.
Kawakubo
Y
Y
Department of Dermatology, School of Medicine, Keio University, Tokyo, Japan.
Manabe
S
S
Yamazoe
Y
Y
Nishikawa
T
T
Kato
R
R
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism*; D006224:Cricetinae; D003600:Cytosol / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D008647:Mesocricetus; D051379:Mice; D009928:Organ Specificity; D051381:Rats; D012867:Skin / Q000201:enzymology*; D013379:Substrate Specificity; D013439:Sulfhydryl Reagents / Q000494:pharmacology
D002273:Carcinogens; D013439:Sulfhydryl Reagents; D000123:Acetyltransferases; D001191:Arylamine N-Acetyltransferase