Partial purification of acetylator phenotype-dependent and independent hamster bladder isozymes with metabolic capacity towards carcinogenic arylamines

Conference · Thu May 01 04:00:00 EDT 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:7186834

Kirlin, W G; Hein, D W; Flammang, T J

Previously they have reported both hepatic and extrahepatic polymorphic expression of acetyl-CoA dependent N-acetyltransferase (NAT) activity in hamster cytosol from homozygous rapid acetylator, homozygous slow acetylator and their F1 progeny. The presence of two distinct NAT isozymes in liver has been implicated as a biochemical basis for the polymorphism. Partial purification of bladder cytosol by ion-exchange chromatography yielded two NAT isozymes with qualitatively similar patterns of activity towards 2-aminofluorene and 4-aminobiphenyl. Both isozymes were present in bladder cytosol of rapid or slow acetylators; the activity of one isozyme was acetylator genotype-dependent, with considerably higher activity in rapid acetylators. The NAT activity of a second isozyme did not appear to vary with acetylator genotype, suggesting that the polymorphism expressed in hamster bladder is primarily due to activity differences of an acetylator genotype dependent isozyme. Both isozymes also catalyzed the acetyl CoA-independent metabolic activation of N-hydroxyacetylaminofluorene as measured by binding to DNA. The polymorphism in bladder NAT activity and the existence of multiple isozymes potentially important for metabolic activation in the bladder may be a factor in formation of DNA-adducts and genetic variation in arylamine carcinogenesis.

• Research Organization: Morehouse School of Medicine, Atlanta, GA
• OSTI ID: 7186834
• Report Number(s): CONF-8606151-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:6
• Country of Publication: United States
• Language: English

Related Subjects

550500 -- Metabolism
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACETYLATION
ACYLATION
ADDUCTS
ANIMALS
AROMATICS
BIPHENYL
BLADDER
BODY
CARCINOGENS
CHEMICAL REACTIONS
CHROMATOGRAPHY
CONDENSED AROMATICS
DNA ADDUCTS
ENZYME ACTIVITY
ENZYMES
FLUORENE
HAMSTERS
HYDROCARBONS
ION EXCHANGE CHROMATOGRAPHY
MAMMALS
METABOLIC ACTIVATION
METABOLISM
ORGANIC COMPOUNDS
ORGANS
PURIFICATION
RODENTS
SEPARATION PROCESSES
TRANSFERASES
URINARY TRACT
VERTEBRATES