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Distribution and metabolism of the natural anticarcinogen phenethyl isothiocyanate in A/J mice
Section of Nucleic Acid Chemistry, Division of Chemical Carcinogenesis, American Health Foundation Valhalla, NY 10595, USA
1To whom correspondence should be addressed
The distribution and metabolism of phenethyl isothiocyanate (PEITC), a naturally occurring anticarcinogen, was investigated in A/J mice. Mice were administered 5 µmol of [14C]PEITC (2 µCi/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.
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