Skip to main content
Log in

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

  • Genotoxicity
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Ayalogu EO, Snelling J, Lewis DFV, Talwa RS, Clifford MN, Ioannides C (1995) Induction of hepatic CYP1A2 by the oral administration of caffeine to rats: lack of association with the Ah locus. Biochim Biophys Acta 1272:89–94

    Article  CAS  PubMed  Google Scholar 

  • Bock KW, White INH (1974) UDP-glucuronyltransferase in perfused rat liver and in microsomes: influence of phenobarbital and 3-methylcholanthrene. Eur J Biochem 46:451–459

    CAS  PubMed  Google Scholar 

  • Bu-Abbas A, Clifford MN, Walker R, Ioannides C (1994) Selective induction of rat hepatic CYP1 and CYP4 proteins and of peroxisomal proliferation by green tea. Carcinogenesis 15:2575–2579

    CAS  PubMed  Google Scholar 

  • Bu-Abbas A, Clifford MN, Ioannides C, Walker R (1995) Stimulation of rat hepatic UDP-glucurorosyl transferase activity following treatment with green tea. Food Chem Toxic 33:27–30

    Article  CAS  Google Scholar 

  • Bu-Abbas A, Clifford MN, Walker R, Ioannides C (1998) Contribution of caffeine and flavanols in the induction of hepatic phase II activities by green tea. Food Chem Toxicol 36:617–621

    Article  CAS  PubMed  Google Scholar 

  • Bu-Abbas A, Clifford MN, Walker R, Ioannides C (1999a) Modulation of hepatic cytochrome P450 activity and carcinogen bioactivation by tea: contribution of caffeine and flavanols. Environ Toxicol Pharmacol 7:41–47

    Article  CAS  Google Scholar 

  • Bu-Abbas A, Dobrota M, Copeland E, Clifford MN, Walker R, Ioannides C (1999b) Proliferation of hepatic peroxisomes in rats following the intake of green or black tea. Toxicol Lett 109:69–76

    Article  CAS  PubMed  Google Scholar 

  • Burke MD, Mayer RT (1974) Ethoxyresorufin: direct fluorimetric assay of a microsomal O-dealkylation which is preferentially inducible by 3-methylcholanthrene. Drug Metab Dispos 2:583–588

    CAS  PubMed  Google Scholar 

  • Burke MD, Mayer RT (1983) Differential effects of phenobarbitone and 3-methylcholanthrene induction on the hepatic microsomal and cytochrome P-450-binding of phenoxazone and a homologous series of its n-alkyl ethers (alkoxyresorufins). Chem Biol Interact 45:243–258

    Article  CAS  PubMed  Google Scholar 

  • Chen L, Bondoc FY, Hussin AHJ, Thomas PE, Yang CS (1996) Caffeine induces cytochrome P4501A2: induction of CYP1A2 by tea in rats. Drug Metab Dispos 24:529–533

    CAS  PubMed  Google Scholar 

  • Embola CW, Weisburger JH, Weisburger MC (2001a) Urinary excretion of N-OH-2-amino-3-methylimidazo[4,5-f]quinoline-N-glucuronide in F344 rats is enhanced by green tea. Carcinogenesis 22:1095–1098

    Article  CAS  PubMed  Google Scholar 

  • Embola CW, Weisburger MC, Weisburger JH (2001b) Green tea and the metabolism of 2-amino-3-methylimidazo[4,5-f]quinoline in F344 rats. Food Chem Toxicol 39:629–633

    Article  CAS  PubMed  Google Scholar 

  • Fujiki H, Suganuma M (2002) Green tea and cancer prevention. Proc Japan Acad B 78:263–270

    Google Scholar 

  • Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferase, the first enzymic step in mercapturic acid formation. J Biol Chem 249:7130–7139

    CAS  PubMed  Google Scholar 

  • Ioannides C, Yoxall V (2003) Antimutagenic activity of tea: role of polyphenols. Curr Opin Clin Nutr Metab Care 6:649–656

    CAS  PubMed  Google Scholar 

  • Jiang T, Glickman BW, de Boer JG (2001) Protective effect of green tea against benzo[a]pyrene-induced mutations in the liver of Big Blue transgenic mice. Mutat Res 480–481:147–151

    Google Scholar 

  • King RS, Teitel CH, Shaddock JG, Casciano DA, Kadlubar FF (1999) Detoxification of carcinogenic aromatic and heterocyclic amines by enzymatic reduction of the N-hydroxy derivative. Cancer Lett 143:167–171

    Article  CAS  PubMed  Google Scholar 

  • Kohlmeier L, Weterings KGC, Steck S, Kok FJ (1997) Tea and cancer prevention: an evaluation of the epdemiologic literature. Nutr Cancer 27:1–13

    CAS  PubMed  Google Scholar 

  • Lin DX, Thompson PA, Teitel C, Chen JS, Kadlubar FF (2003) Direct reduction of N-acetoxy-PhIP by tea polyphenols: a possible mechanism for chemoprevention against PhIP–DNA adduct formation. Mutat Res 523–524:193–200

    Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall AJ (1951) Protein determination with the Folin phenol reagent. J Biol Chem 193:265–271

    CAS  Google Scholar 

  • Maron MD, Ames BN (1983) Revised methods for the Salmonella mutagenicity test. Mutat Res 113:173–215

    PubMed  Google Scholar 

  • McArdle NJ, Clifford MN, Ioannides C (1999) Consumption of tea modulates the urinary excretion of mutagens in rats treated with IQ: role of caffeine. Mutat Res 441:191–203

    Article  CAS  PubMed  Google Scholar 

  • Namkung MJ, Yang HL, Hulla JE, Juchau MR (1988) On the substrate specificity of cytochrome P450IIIA1. Mol Pharmacol 34:628–637

    CAS  PubMed  Google Scholar 

  • Rodrigues AD, Gibson GG, Ioannides C, Parke DV (1987) Interactions of imidazole antifungal agents with purified cytochrome P450 proteins. Biochem Pharmacol 36:4277–4281

    Article  CAS  PubMed  Google Scholar 

  • Rodrigues AD, Ayrton AD, Williams EJ, Lewis DFV, Walker R, Ioannides C (1989) Preferential induction of the rat hepatic P450 I proteins by the food carcinogen 2-amino-3-methyl-4-imidazo (4,5-f) quinoline (IQ). Eur J Biochem 181:627–631

    CAS  PubMed  Google Scholar 

  • Santana-Rios G, Orner GA, Xu M, Izquierdo-Pulido M, Dashwood RH (2001) Inhibition by white tea of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced colonic aberrant crypts in the F344 rat. Nutr Cancer 41:98–103

    CAS  PubMed  Google Scholar 

  • Schut HAJ, Yao R (2000) Tea as a chemopreventive agent in PhIP carcinogenesis: effects of green tea and black tea on PhIP-DNA adduct formation in female F-344 rats. Nutr Cancer 36:52–58

    Article  CAS  PubMed  Google Scholar 

  • Snyderwine EG, Nouso K, Schut HA (1993) Effect of 3-methylcholanthrene induction on the distribution and DNA adduction of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in F344 rats. Food Chem Toxicol 31:415–423

    Article  CAS  PubMed  Google Scholar 

  • Sohn OS, Surace A, Fiala ES, Richie, JP Jr, Colosimo S, Zang E, Weisburger JH (1994) Effects of green and black tea on hepatic xenobiotic metabolizing systems in the male F344 rat. Xenobiotica 24:119–127

    CAS  PubMed  Google Scholar 

  • Suzuki S, Takahashi S, Asamoto M, Inaguma S, Ogiso T, Hirose M, Shirai T (2002) Lack of modification of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)-induces hepatocarcinogenesis in rats by fenbendazole. Cancer Lett 185:39–45

    Article  CAS  PubMed  Google Scholar 

  • Turesky RJ (2002) Heterocyclic aromatic amine metabolism, DNA adduct formation, mutagenesis and carcinogenesis. Drug Metab Rev 34:625–650

    Article  CAS  PubMed  Google Scholar 

  • von Pressentin MDM, Chen M, Guttenplan JB (2001) Mutagenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and N-nitrosonornicotine in lacZ upper aerodigestive tissue and liver and inhibition by green tea. Carcinogenesis 22:203–206

    Article  PubMed  Google Scholar 

  • Wang ZY, Hong JY, Huang M-T, Reuhl KR, Conney AH, Yang CS (1992) Inhibition of N-nitrosodiethylamine- and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced tumorigenesis in A/J mice. Cancer Res 52:1943–1947

    CAS  PubMed  Google Scholar 

  • Wang ZY, Huang M-T, Lou Y-R, Xie J-G, Reuhl KR, Newmark HL, Ho C-T, Yang CS, Conney AH (1994) Inhibitory effects of black tea, green tea, decaffeinated black tea, and decaffeinated green tea on ultraviolet B light-induced skin tumorigenesis in 7,12-dimethylbenz(a)anthracene-initiated SKH-1 mice. Cancer Res 54:3428–3435

    CAS  PubMed  Google Scholar 

  • Xu M, Bailey AC, Hernaez JF, Taoka CR, Schut HAJ, Dashwood RH (1996) Protection by green tea, black tea, and indole-3-carbinol against 4-methylimidazo[4,5-f]quinoline-induced DNA adducts and colonic aberrant crypts in the F344 rat. Carcinogenesis 17:1429–1434

    CAS  PubMed  Google Scholar 

  • Yang CS, Maliakal P, Meng X (2002) Inhibition of carcinogenesis by tea. Annu Rev Pharmacol Toxicol 42:25–54

    Google Scholar 

Download references

Acknowledgements

The authors acknowledge gratefully financial support from the European Union under Framework 4 (POLYBIND project).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to C. Ioannides.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yoxall, V.R., Parker, D.A., Kentish, P.A. et al. 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. Arch Toxicol 78, 477–482 (2004). https://doi.org/10.1007/s00204-004-0562-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-004-0562-3

Keywords

Navigation