In vitro formation and degradation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) protein adducts.
Adduct formation between the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and rat serum albumin (RSA) was studied in vitro using hepatic microsomes isolated from polychlorinated biphenyl-induced rats. With 1-methyl-2-nitro-6-phenylimidazo[4,5-b]pyridine (2-nitro-PhIP) as starting material, four main products were formed. Pretreatment of RSA with beta-mercaptoethanol markedly increased the yield of one of them. In this adduct, the C-2 of PhIP was linked to cysteine of RSA at position 34 in a C-S linkage. With N2-acetoxy-PhIP as starting material, unstable conjugates were formed with RSA as well as with glutathione (GSH) and cysteine. The suggested structures of the GSH and cysteine conjugates, GSH-S-N2-PhIP and cysteine-S-N2-PhIP respectively, are based on mass spectra and UV spectra. The degradation of the conjugates of GSH and cysteine as well as of the protein adduct were monitored. They all resulted in the same degradation product, identified as 2-amino-5-hydroxy-1-methyl-6-phenylimidazo[4,5-b]pyridine (5-hydroxy-PhIP).
Reistad
R
R
National Institute for Consumer Research, Lysaker, Norway.
Frandsen
H
H
Grivas
S
S
Alexander
J
J
D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007093:Imidazoles / Q000378:metabolism*; D009153:Mutagens / Q000378:metabolism*; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism*
D002273:Carcinogens; D007093:Imidazoles; D009153:Mutagens; D012709:Serum Albumin; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D005978:Glutathione; D003545:Cysteine