Urinary excretion levels of carcinogenic glutamic acid pyrolysis products and their N-acetyl derivatives in humans.
The carcinogenic glutamic acid pyrolysis products 2-amino-6-methyldipyrido [1, 2-a: 3', 2'-d]imidazole (Glu-P-1) and 2-amino-dipyrido [1, 2-a: 3', 2'-d] imidazole (Glu-P-2), and their N-acetyl derivatives were measured in 24-h urine of individual subjects by high-performance liquid chromatography. These compounds were detected in all urine samples analyzed, although the contents varied widely among subjects. The mean levels of Glu-P-1, N-acetyl-Glu-P-1, Glu-P-2 and N-acetyl-Glu-P-2 in 24-h urine were 0.53, 0.41, 2.12 and 4.60 pmol, respectively. In vitro experiments revealed N-acetyltransferase activity with Glu-P-1 and Glu-P-2 in the cytosolic fractions from rat kidneys and human autopsy kidney specimens as well as those from liver specimens, suggesting that extrahepatic tissues may also play significant roles in the N-acetylation of these carcinogens. These results show that Glu-P-1 and Glu-P-2, after being partially N-acetylated in metabolic organs such as liver and kidney, are excreted into urine together with their N-acetyl derivatives. It is suggested that daily excretion of carcinogenic glutamic acid pyrolysis products and their N-acetyl derivatives into urine can be a suitable biological monitor for exposure to these carcinogens.


BACKGROUND
Glu-P-1, 2-amino-6-methyldipyrido [1, 2-a: 3', 2'-d] imidazole; Glu-P-2, 2-aminodipyrido [1, 2-a: 3', 2'-d] imidazole; N-acetyl-Glu-P-1, 2-acetylamino-6-methyldipyrido [1, 2-a: 3', 2'-d] imidazole; N-acetyl-Glu-P-2, 2-acetylaminodipyrido[1,2- a:3', 2'-d]imidazole; HPLC, high-performance liquid chromatography.
Kanai
Y
Y
Department of Hygiene and Preventive Medicine, Faculty of Medicine, University of Tokyo.
Wada
O
O
Manabe
S
S
D000107:Acetylation; D000368:Aged; D002273:Carcinogens / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004784:Environmental Monitoring; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006801:Humans; D007093:Imidazoles / Q000652:urine*; D008297:Male
D002273:Carcinogens; D005971:Glutamates; D007093:Imidazoles; C049870:N-acetyl-2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; D018698:Glutamic Acid; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; C023847:Glu-P-2