Distribution and metabolism of the natural anticarcinogen phenethyl isothiocyanate in A/J mice.
The distribution and metabolism of phenethyl isothiocyanate (PEITC), a naturally occurring anticarcinogen, was investigated in A/J mice. Mice were administered 5 mumol of [14C]PEITC (2 microCi/mouse) by gavage and killed at 1, 2, 4, 8, 24, 48 or 72 h after dosing. Radioactivity present in the spleen, heart, liver, lung, kidney, brain, urine and feces was measured. Lung, the target tissue of PEITC inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) lung tumorigenesis, showed maximum radioactivity between 4 and 8 h after dosing, suggesting this time period would be optimal for maximal inhibition by PEITC in A/J mice. Approximately 50% of the total radioactivity was excreted within 24 h after dosing with nearly 80% of radioactivity found in urine and feces at 72 h. Two metabolites were isolated by reverse-phase HPLC from urine of mice treated with PEITC. The identities of these metabolites were determined by comparison with synthetic standards and by NMR and MS. The major metabolite was a cyclic mercaptopyruvic acid conjugate, whereas the minor metabolite was an N-acetylcysteine conjugate. Approximately 25% of the administered dose of PEITC was excreted as the cyclic mercaptopyruvic acid conjugate and 10% as the N-acetylcysteine conjugate. These results suggest that urinary metabolites of PEITC may provide potentially useful dosimeters for this natural anticarcinogen.
Eklind
K I
KI
Division of Chemical Carcinogenesis, American Health Foundation, Valhalla, NY 10595.
Morse
M A
MA
Chung
F L
FL
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005243:Feces; D005260:Female; D017879:Isothiocyanates; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D013861:Thiocyanates / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D014018:Tissue Distribution
D017879:Isothiocyanates; D013861:Thiocyanates; C058305:phenethyl isothiocyanate