Influence of glutathione conjugation on the immunogenicity of dinitrophenyl derivatives in the rat.
The role of metabolic detoxication (glutathione conjugation) in the humoral response to three model haptens, dinitrofluorobenzene (DNFB), dinitrochlorobenzene (DNCB) and dinitrobenzenesulphonate (DNBS), was investigated in male Wistar rats. All three haptens produced a measurable anti-dinitrophenyl IgG antibody response over a wide dose range (2.7 nmol/kg to 0.27 mmol/kg) given for 4 days. A significant difference in antibody titre was only observed at the highest dose (DNFB greater than DNCB = DNBS), despite a marked difference in reactivity towards a protein carrier (albumin) and N-acetyl-lysine in vitro. These observations can be partly explained by the fact that the most reactive hapten (DNFB) conjugates most rapidly with glutathione in vitro and in vivo.
Tingle
M D
MD
Department of Pharmacology and Therapeutics, University of Liverpool, UK.
Clarke
J B
JB
Kitteringham
N R
NR
Park
B K
BK
D000818:Animals; D000941:Antigens / Q000032:analysis; D004136:Dinitrobenzenes / Q000276:immunology* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D007074:Immunoglobulin G / Q000032:analysis; D008658:Inactivation, Metabolic; D008297:Male; D009578:Nitrobenzenes / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains
D000941:Antigens; D004136:Dinitrobenzenes; D007074:Immunoglobulin G; D009578:Nitrobenzenes; D005978:Glutathione