Polymorphic and monomorphic expression of arylamine carcinogen N-acetyltransferase isozymes in tumor target organ cytosols of Syrian hamsters congenic at the polymorphic acetyltransferase locus.
A number of human epidemiological investigations suggest a relationship between acetylator phenotype and the incidence and/or severity of tumors caused by exposure to arylamine carcinogens. Conclusions drawn from these investigations can be compromised by a variety of environmental and other genetic factors. To eliminate variability in these other factors, our laboratory recently completed construction of homozygous rapid (Bio. 82.73/H-Patr), heterozygous intermediate (Bio. 82.73/H-Patr/Pat(s)) and homozygous slow (Bio. 82.73/H-Pat(s)) acetylator congenic hamsters. The purpose of the present study was to assess the utility of this congenic hamster model for investigations into the relationship between acetylator genotype and arylamine carcinogenesis. We report the expression of acetylator genotype-dependent (polymorphic) and acetylator genotype-independent (monomorphic) N-acetyltransferase isozymes in hepatic cytosols. The hepatic polymorphic N-acetyltransferase isozyme isolated from the congenic hamsters expressed clearly acetylator-genotype dependent (Patr greater than Patr/Pat(s) greater than Pat(s)) N-acetylation towards p-aminobenzoic acid, 4-aminobiphenyl, 2-aminofluorene, p-aminophenol, 1-aminopyrene, 5-aminosalicylic acid, beta-naphthylamine, 3,4-dichloroaniline, 3,2'-dimethyl-4-aminobiphenyl and p-phenetidine. Acetylator genotype-dependent N-acetylation for a number of arylamines also was observed in liver, colon, kidney and urinary bladder cytosols derived from the congenic hamster lines, including arylamines highly carcinogenic to hamster colon and urinary bladders. It is concluded that the congenic hamster model will be useful in studies to delineate the role of acetylator genotype in the incidence or severity of arylamine tumors.
Hein
D W
DW
Department of Pharmacology, University of North Dakota School of Medicine, Grand Forks.
Rustan
T D
TD
Bucher
K D
KD
Miller
L S
LS
D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism*; D003106:Colon / Q000201:enzymology; D006224:Cricetinae; D003600:Cytosol / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D008647:Mesocricetus; D011110:Polymorphism, Genetic / Q000235:genetics*; D001743:Urinary Bladder / Q000201:enzymology
D002273:Carcinogens; D007527:Isoenzymes; D001191:Arylamine N-Acetyltransferase