Short-term black tea intake modulates the excretion of urinary mutagens in rats treated with 2-amino-3-methylimidazo-[4,5-f]quinoline (IQ): role of CYP1A2 upregulation.
Rats were exposed to black tea (2.5% w/v) as their sole drinking liquid for either 1 day or 1 month, while controls were maintained on water. After this treatment period, all animals received a single oral dose IQ (2-amino-3-methylimidazo-[4,5-f]quinoline), and urine was collected for 48 h. Mutagenic activity of the urine was determined in the Ames test in the presence and absence of an activation system. The excretion of direct-acting mutagens was markedly reduced following tea intake, and was more pronounced after the 1-day treatment. Similarly, both tea treatments suppressed the excretion of indirect-acting mutagens. Furthermore, both tea treatments induced hepatic CYP1A2 activity and expression, but cytosolic glutathione S-transferase activity was only modestly induced in the group of animals receiving tea for 1 day, and only when DCNB (1,2-dichloro-4-nitrobenzene) was used as substrate; glucuronosyl activity was elevated modestly only in the animals receiving the tea for a month. It is concluded that even short-term exposure to black tea is capable of influencing the metabolic fate of IQ, and this is most likely related to the upregulation of CYP1A2.
Yoxall
V R
VR
Molecular Toxicology Group, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK.
Parker
D A
DA
Kentish
P A
PA
Ioannides
C
C
D000818:Animals; D002273:Carcinogens / Q000493:pharmacokinetics*; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis* / Q000235:genetics; D003600:Cytosol / Q000201:enzymology; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000493:pharmacokinetics*; D009578:Nitrobenzenes / Q000378:metabolism; D011804:Quinolines / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013662:Tea; D015854:Up-Regulation / Q000502:physiology; D015430:Weight Gain / Q000187:drug effects
D002273:Carcinogens; D009153:Mutagens; D009578:Nitrobenzenes; D011804:Quinolines; D013662:Tea; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C028328:1,2-dichloro-4-nitrobenzene; D006899:Mixed Function Oxygenases; D019388:Cytochrome P-450 CYP1A2; D005982:Glutathione Transferase