Characterization of antimutagenic mechanism of 3-allyl-5-substituted 2-thiohydantoins against 2-amino-3-methylimidazo[4,5-f]quinoline.
3-Allyl-5-substituted 2-thiohydantoins (ATH-amino acids) derived from allyl isothiocyanate and amino acids can inhibit the mutagenicity of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in the Salmonella assay. In this report, we studied possible mechanisms for the inhibition using rat liver S9 in assays for ethoxyresorufin O-deethylase (EROD), a marker activity for cytochrome P450 1A (CYP1A), which activates heterocyclic amines, and the Salmonella assays with the direct-acting mutagen 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline (N-hydroxy-IQ). Quantitative analysis of ATH-amino acids and IQ during incubation with rat liver S9 fraction by HPLC showed that ATH-amino acids could act as S9-inhibitors, thereby inhibiting metabolic activation of IQ. Among the tested ATH-amino acids, ATH-Phe, ATH-Trp, ATH-Leu and ATH-Val showed a dose-dependent inhibition of EROD activity. ATH-Gly, ATH-Glu, and ATH-Asp behaved as blocking agents toward N-hydroxy-IQ, but exhibited no inhibition of EROD activity.
Takahashi
Asaka
A
Nagano Prefectural College, 8-49-7 Miwa, Nagano 380-8525, Japan. asaka@nagano-kentan.ac.jp
Matsuoka
Hiroki
H
Yamada
Keiichi
K
Uda
Yasushi
Y
D000818:Animals; D015415:Biomarkers; D019363:Cytochrome P-450 CYP1A1 / Q000032:analysis / Q000494:pharmacology; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000201:enzymology; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism* / Q000633:toxicity*; D011804:Quinolines / Q000378:metabolism* / Q000633:toxicity*; D051381:Rats; D012475:Salmonella / Q000235:genetics; D013867:Thiohydantoins / Q000494:pharmacology*
D015415:Biomarkers; D009153:Mutagens; D011804:Quinolines; D013867:Thiohydantoins; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D019363:Cytochrome P-450 CYP1A1