Characterization of acetylator genotype-dependent and -independent hamster hepatic n-acetyltransferases and their role in the metabolism of arylamine and n-hydroxyarylamine carcinogens

摘要

An inbred hamster model for the human acetyIation polymorphism was used to investigate the biochemical basis for the acetyIation polymorphism and its relationship with the liver cytosolic enzymes arylamine N-acetyItransferase (NAT), N-hydroxyarylamine 0-acetyltransferase (OAT), and arylhydroxamic acid N,0-acyItransferase (N,O-AT). NAT and OAT activities were examined in liver cytosols derived from homozygous rapid and homozygous slow acetylator hamsters, respectively. Partial purification of hepatic NAT activity indicated the presence of two distinct NAT isozynes in each acetylator genotype. One isozyme was designated polymorphic acetyItransferase (PAT); whereas, the other isozyme was termed monomorphic acetyItransferase (MAT). Kinetic analysis showed that the acetyI at ion polymorphism is primarily due to structural variants of the PAT isozyme. Results from this model may be extrapolated to the human acetyIation polymorphism.