Oxidative conversion by rat liver microsomes of 2-naphthyl isothiocyanate to 2-naphthyl isocyanate, a genotoxicant.
The present study investigated the oxidative metabolism of 2-naphthyl isothiocyanate catalyzed by rat liver microsomes. Incubation of 2-naphthyl isothiocyanate, microsomes, and NADPH yielded either N,N'-di-2-naphthylurea or, on inclusion of 2-aminofluorene in the incubations, N-2-naphthyl-N'-2-fluorenylurea. These ureas were formed by the production of 2-naphthyl isocyanate, which reacted with its hydrolysis product, 2-aminonaphthalene, to yield the symmetrical urea or, with 2-aminofluorene, to form the mixed urea. Formation of N,N'-di-2-naphthylthiourea was also observed, since 2-aminonaphthalene reacted with the substrate. Urea formation was dependent on microsomes, NADPH, and O2. Use of microsomes from rats previously treated with Aroclor increased urea formation > or = 10-fold. The enzyme activity was inhibited by alpha-naphthoflavone, flavone, or CO and slightly inhibited by metyrapone, 7-ethoxycoumarin, or SKF-525A. It was not inhibited by methimazole or paraoxon. These data are consistent with a cytochrome P-450-dependent, oxidative desulfuration of the isothiocyanate to yield an isocyanate.
Lee
M S
MS
Department of Chemical Carcinogenesis, Michigan Cancer Foundation, Detroit 48201.
D015058:1-Naphthylisothiocyanate / Q000378:metabolism*; D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D001711:Biotransformation; D002273:Carcinogens / Q000494:pharmacology; D020111:Chlorodiphenyl (54% Chlorine); D002855:Chromatography, Thin Layer; D003485:Cyanates / Q000378:metabolism*; D017953:Isocyanates; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D009153:Mutagens / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D009281:Naphthalenes / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011916:Rats, Inbred F344; D013056:Spectrophotometry, Ultraviolet
D001140:Aroclors; D002273:Carcinogens; D003485:Cyanates; D017953:Isocyanates; D009153:Mutagens; D009281:Naphthalenes; D020111:Chlorodiphenyl (54% Chlorine); C066450:2-naphthyl isocyanate; D009249:NADP; D015058:1-Naphthylisothiocyanate; C031287:2-naphthylisothiocyanate