title: Exposure to isothiocyanates suppresses urinary mutagenicity in rats treated with heterocyclic amine IQ: lack of association with CYP1 activity.
abstract: The principal objectives of this study were to evaluate whether exposure of rats to low doses of isothiocyanates modulates the overall metabolism of heterocyclic amine 2-amino-3-methylimidazo-[4,5-f]quinoline (IQ), as exemplified by urinary mutagenicity, a food carcinogen, and to relate any modifications in metabolism to changes in CYP1 and glutathione S-transferase activities. Animals were exposed to isothiocyanates either for 2 wk (long-term) or 1 day (short-term), and all animals were then treated with a single oral dose of IQ, and urine was collected daily for 3 days; animals continued to receive the isothiocyanates during this period. Urinary mutagenic activity was determined using the Ames mutagenicity assay in the presence of an activation system from Aroclor 1254-treated rats. At the end of the study, animals were killed and hepatic methoxy- and ethoxyresorufin dealkylations were determined as well as glutathione S-transferase activity. All isothiocyanates studied, namely sulforaphane, erucin, and phenethyl isothiocyanate, decreased urinary mutagenic activity, implying enhanced IQ metabolism, but only after long-term intake. Changes in mutagenic activity were not related to changes of any of the enzyme activities determined. It is concluded that long-term intake of isothiocyanates may stimulate the metabolism of IQ, but this effect is not linked to changes in hepatic CYP1A2 and glutathione S-transferase activities.
authors.affiliation: Centre of Toxicology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK.
authors.forename: Natalya
authors.initials: N
authors.lastname: Hanlon
authors.forename: Nattaya
authors.initials: N
authors.lastname: Konsue
authors.forename: Nick
authors.initials: N
authors.lastname: Coldham
authors.forename: Maurice J
authors.initials: MJ
authors.lastname: Sauer
authors.forename: Costas
authors.initials: C
authors.lastname: Ioannides
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002273:Carcinogens / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2; D003580:Cytochromes / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology*; D008099:Liver / Q000473:pathology; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism*; D011804:Quinolines / Q000633:toxicity / Q000652:urine*; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000494:pharmacology*; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D002273:Carcinogens; D003580:Cytochromes; D017879:Isothiocyanates; D009153:Mutagens; D011804:Quinolines; D013440:Sulfides; D013454:Sulfoxides; D013861:Thiocyanates; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C037152:isothiocyanic acid; C058305:phenethyl isothiocyanate; C073539:erucin; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D005982:Glutathione Transferase; C016766:sulforaphane