RT Journal Article SR Electronic T1 Phenotype of the Most Common “Slow Acetylator” Arylamine N-Acetyltransferase 1 Genetic Variant (NAT1*14B) Is Substrate-Dependent JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 198 OP 204 DO 10.1124/dmd.111.041855 VO 40 IS 1 A1 Lori M. Millner A1 Mark A. Doll A1 Jian Cai A1 J. Christopher States A1 David W. Hein YR 2012 UL http://dmd.aspetjournals.org/content/40/1/198.abstract AB Human arylamine N-acetyltransferase 1 (NAT1) is a phase II cytosolic enzyme responsible for the activation or deactivation of many arylamine compounds including pharmaceuticals and environmental carcinogens. NAT1 is highly polymorphic and has been associated with altered risk toward many cancers. NAT1*14B is characterized by a single nucleotide polymorphism in the coding region (rs4986782; 560G>A; R187Q). NAT1*14B is associated with higher frequency of smoking-induced lung cancer and is the most common “slow acetylator” arylamine NAT1 genetic variant. Previous studies have reported decreased N- and O-acetylation capacity and increased proteasomal degradation of NAT1 14B compared with the referent, NAT1 4. The current study is the first to investigate NAT1*14B expression using constructs that completely mimic NAT1 mRNA by including the 5′- and 3′-untranslated regions, together with the open reading frame of the referent, NAT1*4, or variant, NAT1*14B. Our results show that NAT1 14B is not simply associated with “slow acetylation.” NAT1 14B-catalyzed acetylation phenotype is substrate-dependent, and NAT1 14B exhibits higher N- and O-acetylation catalytic efficiency as well as DNA adducts after exposure to the human carcinogen 4-aminobiphenyl.