Black tea intake modulates the excretion of urinary mutagens in rats exposed to 6-aminochrysene: induction of cytochromes P450 by 6-aminochrysene in the rat.
Rats were exposed to black tea (2.5% w/v) as their sole drinking liquid for either 1 day (short-term) or 1 month (long-term), while controls received water. After exposure, all animals received a single oral dose of 6-aminochrysene and urine was collected for 72 h. Urinary mutagenicity was determined in the Ames test using an activation system comprising hepatic cytosol from Aroclor 1254-induced rats and utilizing the Salmonella typhimurium O-acetylase overexpressing bacterial strain YG1024. Both tea treatments suppressed the urinary excretion of indirect acting mutagens; no direct acting mutagenic activity was detectable. Furthermore, both tea treatments induced hepatic CYP1A2 activity, as exemplified by the O-demethylation of methoxyresorufin, when compared with the corresponding controls; similarly, an increase in CYP1A2 apoprotein levels was observed. The O-depentylation of pentoxyresorufin was also induced by the long-term tea treatment only, but the effect was less pronounced. No significant changes were seen in glutathione S-transferase and glucuronosyl transferase activities. When rats were exposed to caffeine at a dose level corresponding to that in black tea, a marked decrease was observed in the urinary excretion of indirect acting mutagens following a single oral dose of 6-aminochrysene. It is concluded that even after short-term exposure, black tea enhances the metabolism of 6-aminochrysene and that this is probably related to the up-regulation of hepatic CYP1A2 by the caffeine present in black tea. Finally, 6-aminochrysene was a potent inducer of CYP1A1, as assessed by the O-deethylation of ethoxyresorufin and immunoblot analysis. The same treatment modestly increased glutathione S-transferase activity when assessed using 1-chloro-2,4-dinitrobenzene as the accepting substrate.
Yoxall
Victoria
V
Molecular Toxicology Group, School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK.
Umachandran
Meera
M
Wilson
Judith
J
Kentish
Peter
P
Ioannides
Costas
C
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002911:Chrysenes / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D009153:Mutagens / Q000378:metabolism*; D051381:Rats; D013662:Tea / Q000378:metabolism*; D014556:Urine / Q000502:physiology
D000970:Antineoplastic Agents; D002911:Chrysenes; D009153:Mutagens; D013662:Tea; D003577:Cytochrome P-450 Enzyme System; C100101:6-chrysenamine