Evaluation of 4-(N-methylnitrosamino)-4-(3-pyridyl)butyric acid as a potential monitor of endogenous nitrosation of nicotine and its metabolites.
The potential endogenous nitrosation of nicotine and cotinine to yield 4-(N-methylnitrosamino)-4-(3-pyridyl)butyric acid (Iso-NNAC) has been studied in smokers and non-smokers. Following i.v. administration of 100 micrograms Iso-NNAC to rats, excretion in urine (67.4 +/- 25.4%) and feces (6.1 +/- 1.6%) occurred within 24 h. The urinary excretion of nitrate, nicotine, cotinine and Iso-NNAC were determined in 24 h urine samples from 19 smokers and 10 non-smokers. Iso-NNAC excretion was found on four occasions (44, 65, 74 and 163 ng/day) in smokers; non-smokers did not excrete Iso-NNAC. Oral administration of nicotine (n = 8; 12-40 mg) and cotinine (n = 3; 40-60 mg) to abstinent smokers did not result in Iso-NNAC excretion, even after oral nitrate (150 mg) supplementation. However, Iso-NNAC was found in cigarette tobacco (10-330 ng/g) and mainstream cigarette smoke (1.1-5.5 ng/cig.). Our studies suggest that the occasional presence of Iso-NNAC in smokers' urine results from exogenous exposure to the preformed compound in mainstream cigarette smoke and not from endogenous nitrosation of nicotine and its metabolites.
Tricker
A R
AR
Analytisch-biologisches Forschungslabor, Munich, Germany.
Scherer
G
G
Conze
C
C
Adlkofer
F
F
Pachinger
A
A
Klus
H
H
D000284:Administration, Oral; D000328:Adult; D000818:Animals; D002849:Chromatography, Gas; D003367:Cotinine / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000378:metabolism*; D009602:Nitrosamines / Q000652:urine*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012907:Smoking / Q000652:urine
D009602:Nitrosamines; C060946:4-(methylnitrosamino)-4-(3-pyridyl)butyric acid; D009538:Nicotine; D003367:Cotinine