title: Further investigations of the role of acetylation in sulphonamide hypersensitivity reactions.
abstract: Abstract Sulphonamide hypersensitivity reactions are believed to be mediated through reactive intermediates derived from oxidation of the paraamino group to form sulphonamide hydroxylamines. Sulphamethoxazole hydroxylamine (SMX-HA) can be acetylated by N-acetyltransferase (NAT) enzymes to form an acetoxy metabolite (acetoxySMX). In the current studies, acetoxySMX was found to be not toxic over the concentration range of 0 to 500 μM towards a human lymphoblastoid cell line (RPMI 1788) or a human hepatoma cell line (HepG2). Further, transient expression of NAT1 in COS-1 cells or stable transfection of NAT1 andNAT2 in HepG2 cells did not alter the toxicity of SMX-HA in vitro. The activity of NAT1 in isolated mononuclear leucocytes (a reflection of systemic NAT1 activity) determined with paraaminobenzoic acid as a substrate was not different between controls (n = 11) or patients with a known hypersensitivity reaction (n = 5) (4.1 ±1.2 nmol min(-1)mg(-1) vs 5.7 ± 1.4 nmol min(-1) mg(-1)). Thus, acetoxy SMX is unlikely to play a significant role in mediating SMX hypersensitivity reactions anda constitutive deficiency in NAT1 activity is not a common finding in patients susceptible to SMX hypersensitivity reactions.
authors.forename: C E
authors.initials: CE
authors.lastname: Nuss
authors.forename: D M
authors.initials: DM
authors.lastname: Grant
authors.forename: S P
authors.initials: SP
authors.lastname: Spielberg
authors.forename: A E
authors.initials: AE
authors.lastname: Cribb