Apiaceous vegetable constituents inhibit human cytochrome P-450 1A2 (hCYP1A2) activity and hCYP1A2-mediated mutagenicity of aflatoxin B1

Food and Chemical Toxicology

Volumn 44, Issue 9, 2006, Pages 1474-1484

  Peterson, Sabrina ^a,b   Lampe, Johanna W ^a,b   Bammler, Theo K ^a   Gross Steinmeyer, Kerstin ^a   Eaton, David L ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

^b USA   (United States)

Author keywords

Aflatoxin; Apiaceae; Carrot; CYP1A2; Flavonoid; Furanocoumarin

Indexed keywords

AFLATOXIN B1; APIGENIN; BERGAPTEN; CAFFEIC ACID; CHLOROGENIC ACID; CYTOCHROME P450 1A2; CYTOCHROME P450 INHIBITOR; METHOXSALEN; NARINGENIN; PLANT MEDICINAL PRODUCT; PSORALEN; QUERCETIN;

ALLELE; ARTICLE; AUXOTROPHY; CELL SURVIVAL; CONTROLLED STUDY; DIPLOIDY; DRUG EFFECT; DRUG SCREENING; ENZYME ACTIVITY; ENZYME ASSAY; ENZYME INHIBITION; FOOD INTAKE; GENE CONVERSION; GENE MUTATION; HETEROLOGOUS EXPRESSION; IN VIVO STUDY; MICROSOME; MUTAGENICITY; NONHUMAN; PROTEIN EXPRESSION; SACCHAROMYCES CEREVISIAE; STATISTICAL SIGNIFICANCE; VEGETABLE; YEAST;

AFLATOXIN B1; APIACEAE; BIOTRANSFORMATION; CELL SURVIVAL; CYTOCHROME P-450 CYP1A2; CYTOCHROME P-450 ENZYME SYSTEM; ENZYME INHIBITORS; FLAVONOIDS; HUMANS; INHIBITORY CONCENTRATION 50; MICROSOMES; MUTAGENS; OXIDOREDUCTASES; PLANT EXTRACTS; POISONS; PSORALENS; RECOMBINATION, GENETIC; SACCHAROMYCES CEREVISIAE;

APIUM GRAVEOLENS VAR. DULCE; DAUCUS CAROTA; PETROSELINUM CRISPUM; SACCHAROMYCES CEREVISIAE;

EID: 33745617086     PISSN: 02786915     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.fct.2006.04.010     Document Type: Article

References (73)

1. Baer-Dubowska W., Szaefer H., and Krajka-Kuzniak V. Inhibition of murine hepatic cytochrome P450 activities by natural and synthetic phenolic compounds. Xenobiotica 28 (1998) 735-743
2. Beier R.C. Natural pesticides and bioactive components in foods. Rev. Environ. Contam. Toxicol. 113 (1990) 47-137
3. Bejaoui H., Mathieu F., Taillandier P., and Lebrihi A. Ochratoxin A removal in synthetic and natural grape juices by selected oenological Saccharomyces strains. J. Appl. Microbiol. 97 (2004) 1038-1044
4. Bendriss E.K., Bechtel Y., Bendriss A., Humbert P.H., Paintaud G., Magnette J., Agache P., and Bechtel P.R. Inhibition of caffeine metabolism by 5-methoxypsoralen in patients with psoriasis. Br. J. Clin. Pharmacol. 41 (1996) 421-424
5. Bhattacharya R.K., and Firozi P.F. Effect of plant flavonoids on microsome catalyzed reactions of aflatoxin B1 leading to activation and DNA adduct formation. Cancer Lett. 39 (1988) 85-91
6. Bogaards J.J., Bertrand M., Jackson P., Oudshoorn M.J., Weaver R.J., van Bladeren P.J., and Walther B. Determining the best animal model for human cytochrome P450 activities: a comparison of mouse, rat, rabbit, dog, micropig, monkey and man. Xenobiotica 30 (2000) 1131-1152
7. Boobis A.R., Lynch A.M., Murray S., de la Torre R., Solans A., Farre M., Segura J., Gooderham N.J., and Davies D.S. CYP1A2-catalyzed conversion of dietary heterocyclic amines to their proximate carcinogens is their major route of metabolism in humans. Cancer Res. 54 (1994) 89-94
8. Breinholt V.M., Offord E.A., Brouwer C., Nielsen S.E., Brøsen K., and Friedberg T. In vitro investigation of cytochrome P450-mediated metabolism of dietary flavonoids. Food Chem. Toxicol. 40 (2002) 609-616
9. Busby Jr. W.F., Ackermann J.M., and Crespi C.L. Effect of methanol, ethanol, dimethyl sulfoxide, and acetonitrile on in vitro activities of cDNA-expressed human cytochromes P-450. Drug Metab. Dispos. 27 (1999) 246-249
10. Cai Y., Bennett D., Nair R.V., Ceska O., Ashwood-Smith M.J., and DiGiovanni J. Inhibition and inactivation of murine hepatic ethoxy- and pentoxyresorufin O-dealkylase by naturally occurring coumarins. Chem. Res. Toxicol. 6 (1993) 872-879
11. Del Carratore R., Morichetti E., Bronzetti G., and Galeotti C. Induction of cytochrome P-450 by 5-methoxypsoralen in the yeast Saccharomyces cerevisiae. J. Environ. Pathol. Toxicol. Oncol. 13 (1994) 227-230
12. Dierks E.A., Stams K.R., Lim H.K., Cornelius G., Zhang H., and Ball S.E. A method for the simultaneous evaluation of the activities of seven major human drug-metabolizing cytochrome P450s using an in vitro cocktail of probe substrates and fast gradient liquid chromatography tandem mass spectrometry. Drug Metab. Dispos. 29 (2001) 23-29
13. Draper A.J., Madan A., and Parkinson A. Inhibition of coumarin 7-hydroxylase activity in human liver microsomes. Arch. Biochem. Biophys. 341 (1997) 47-61
14. Duke, J. A., 2004. Dr. Duke's Phytochemical and Ethnobotanical Databases [on the Internet]. Washington, DC: Agricultural Research Service [updated 2004 April 28; cited 2005 July 8]. Available from: .
15. Eagling V.A., Tjia J.F., and Back D.J. Differential selectivity of cytochrome P450 inhibitors against probe substrates in human and rat liver microsomes. Br. J. Clin. Pharmacol. 45 (1998) 107-114
16. Easterbrook J., Lu C., Sakai Y., and Li A.P. Effects of organic solvents on the activities of cytochrome P450 isoforms, UDP-dependent glucuronyl transferase, and phenol sulfotransferase in human hepatocytes. Drug Metab. Dispos. 29 (2001) 141-144
17. Eaton D.L., Bammler T.K., and Kelly E.J. Interindividual differences in response to chemoprotection against aflatoxin-induced hepatocarcinogenesis: implications for human biotransformation enzyme polymorphisms. Adv. Exp. Med. Biol. 500 (2001) 559-576
18. Engel P.C. Outline Studies in Biology (1981), Chapman and Hall, New York
19. Erlund I., Meririnne E., Alfthan G., and Aro A. Plasma kinetics and urinary excretion of the flavanones naringenin and hesperetin in humans after ingestion of orange juice and grapefruit juice. J. Nutr. 131 (2001) 235-241
20. Eugster H.P., and Sengstag C. Saccharomyces cerevisiae: an alternative source for human microsomal liver enzymes and its use in drug interaction studies. Toxicology 82 (1993) 61-73
21. Eugster H.P., Sengstag C., Meyer U.A., Hinnen A., and Wurgler F.E. Constitutive and inducible expression of human cytochrome P450IA1 in yeast Saccharomyces cerevisiae: an alternative enzyme source for in vitro studies. Biochem. Biophys. Res. Commun. 172 (1990) 737-744
22. Fuhr U., Klittich K., and Staib A.H. Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man. Br. J. Clin. Pharmacol. 35 (1993) 431-436
23. Gallagher E.P., Kunze K.L., Stapleton P.L., and Eaton D.L. The kinetics of aflatoxin B1 oxidation by human cDNA-expressed and human liver microsomal cytochromes P450 1A2 and 3A4. Toxicol. Appl. Pharmacol. 141 (1996) 595-606
24. Gross-Steinmeyer K., Stapleton P.L., Tracy J.H., Bammler T.K., Lehman T., Strom S.C., and Eaton D.L. Influence of Matrigel-overlay on constitutive and inducible expression of nine genes encoding drug-metabolizing enzymes in primary human hepatocytes. Xenobiotica 35 (2005) 419-438
25. Guo Y., Breeden L.L., Zarbl H., Preston B.D., and Eaton D.L. Expression of a human cytochrome P450 in yeast permits analysis of pathways for response to and repair of aflatoxin-induced DNA damage. Mol. Cell. Biol. 25 (2005) 5823-5833
26. Hollman P.C., van Trijp J.M., Buysman M.N., van der Gaag M.S., Mengelers M.J., de Vries J.H., and Katan M.B. Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man. FEBS Lett. 418 (1997) 152-156
27. Hussein H.S., and Brasel J.M. Toxicity, metabolism, and impact of mycotoxins on humans and animals. Toxicology 167 (2001) 101-134
28. Huwig A., Freimund S., Käppeli O., and Dutler H. Mycotoxin detoxication of animal feed by different adsorbents. Toxicol Lett. 122 (2001) 179-188
29. Ivie G.W., Holt D.L., and Ivey M.C. Natural toxicants in human foods: psoralens in raw and cooked parsnip root. Science 213 (1981) 909-910
30. Kelly E.J., Erickson K.E., Sengstag C., and Eaton D.L. Expression of human microsomal epoxide hydrolase in Saccharomyces cerevisiae reveals a functional role in aflatoxin B1 detoxification. Toxicol. Sci. 65 (2002) 35-42
31. Kensler T.W. Chemoprevention by inducers of carcinogen detoxication enzymes. Environ. Health Perspect. 105 Suppl. 4 (1997) 965-970
32. Kensler T.W., Egner P.A., Dolan P.M., Groopman J.D., and Roebuck B.D. Mechanism of protection against aflatoxin tumorigenicity in rats fed 5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz) and related 1,2-dithiol-3-thiones and 1,2-dithiol-3-ones. Cancer Res. 47 (1987) 4271-4277
33. Klotz A.V., Stegeman J.J., and Walsh C. An alternative 7-ethoxyresorufin O-deethylase activity assay: a continuous visible spectrophotometric method for measurement of cytochrome P-450 monooxygenase activity. Anal. Biochem. 140 (1984) 138-145
34. Koenigs L.L., and Trager W.F. Mechanism-based inactivation of cytochrome P450 2B1 by 8-methoxypsoralen and several other furanocoumarins. Biochemistry 37 (1998) 13184-13193
35. Koenigs L.L., and Trager W.F. Mechanism-based inactivation of P450 2A6 by furanocoumarins. Biochemistry 37 (1998) 10047-10061
36. Kunze K.L., and Trager W.F. Isoform-selective mechanism-based inhibition of human cytochrome P450 1A2 by furafylline. Chem. Res. Toxicol. 6 (1993) 649-656
37. Lampe J.W., King I.B., Li S., Grate M.T., Barale K.V., Chen C., Feng Z., and Potter J.D. Brassica vegetables increase and apiaceous vegetables decrease cytochrome P450 1A2 activity in humans: changes in caffeine metabolite ratios in response to controlled vegetable diets. Carcinogenesis 21 (2000) 1157-1162
38. Langouet S., Coles B., Morel F., Becquemont L., Beaune P., Guengerich F.P., Ketterer B., and Guillouzo A. Inhibition of CYP1A2 and CYP3A4 by oltipraz results in reduction of aflatoxin B1 metabolism in human hepatocytes in primary culture. Cancer Res. 55 (1995) 5574-5579
39. Lee H., Yeom H., Kim Y.G., Yoon C.N., Jin C., Choi J.S., Kim B.R., and Kim D.H. Structure-related inhibition of human hepatic caffeine N3-demethylation by naturally occurring flavonoids. Biochem. Pharmacol. 55 (1998) 1369-1375
40. Lombaert G.A., Siemens K.H., Pellaers P., Mankotia M., and Ng W. Furanocoumarins in celery and parsnips: method and multiyear Canadian survey. J. AOAC Int. 84 (2001) 1135-1143
41. Mäenpää J., Sigusch H., Raunio H., Syngelma T., Vuorela P., Vuorela H., and Pelkonen O. Differential inhibition of coumarin 7-hydroxylase activity in mouse and human liver microsomes. Biochem. Pharmacol. 45 (1993) 1035-1042
42. Malfatti M.A., and Felton J.S. N-glucuronidation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and N-hydroxy-PhIP by specific human UDP-glucuronosyltransferases. Carcinogenesis 22 (2001) 1087-1093
43. Mays D.C., Camisa C., Cheney P., Pacula C.M., Nawoot S., and Gerber N. Methoxsalen is a potent inhibitor of the metabolism of caffeine in humans. Clin. Pharmacol. Ther. 42 (1987) 621-626
44. Moon Y.J., Wang X., and Morris M.E. Dietary flavonoids: effects on xenobiotic and carcinogen metabolism. Toxicol. in Vitro 20 (2006) 187-210
45. Morichetti E., Ceragioli C., Cundari E., Del Carratore R., Fiorio R., Bronzetti G., and Averbeck D. Metabolism of 5-methoxypsoralen by Saccharomyces cerevisiae. Photochem. Photobiol. 54 (1991) 689-695
46. Omura T., and Sato R. The carbon monoxide-binding pigment of liver microsomes. Ii. Solubilization, purification, and properties. J. Biol. Chem. 239 (1964) 2379-2385
47. Ono S., Hatanaka T., Hotta H., Satoh T., Gonzalez F.J., and Tsutsui M. Specificity of substrate and inhibitor probes for cytochrome P450s: evaluation of in vitro metabolism using cDNA-expressed human P450s and human liver microsomes. Xenobiotica 26 (1996) 681-693
48. Ostertag E., Becker T., Ammon J., Bauer-Aymanns H., and Schrenk D. Effects of storage conditions on furocoumarin levels in intact, chopped, or homogenized parsnips. J. Agric. Food. Chem. 50 (2002) 2565-2570
49. Pastrakuljic A., Tang B.K., Roberts E.A., and Kalow W. Distinction of CYP1A1 and CYP1A2 activity by selective inhibition using fluvoxamine and isosafrole. Biochem. Pharmacol. 53 (1997) 531-538
50. Prognon P., Blais J., Vigny P., Averbeck D., Averbeck S., and Gond A. The metabolism of 8-methoxypsoralen by Saccharomyces cerevisiae. Evidence for an inducing effect of ethanol. Farmaco [Sci] 39 (1984) 739-751
51. Salbe A.D., and Bjeldanes L.F. Effect of diet and route of administration on the DNA binding of aflatoxin B1 in the rat. Carcinogenesis 10 (1989) 629-634
52. San R.H., and Chan R.I. Inhibitory effect of phenolic compounds on aflatoxin B1 metabolism and induced mutagenesis. Mutat Res. 177 (1987) 229-239
53. Schiestl R.H., and Gietz R.D. High efficiency transformation of intact yeast cells using single stranded nucleic acids as a carrier. Curr. Genet. 16 (1989) 339-346
54. Sengstag C., and Wurgler F.E. DNA recombination induced by aflatoxin B1 activated by cytochrome P450 1A enzymes. Mol. Carcinogen. 11 (1994) 227-235
55. Sesardic D., Boobis A.R., Murray B.P., Murray S., Segura J., de la Torre R., and Davies D.S. Furafylline is a potent and selective inhibitor of cytochrome P450IA2 in man. Br. J. Clin. Pharmacol. 29 (1990) 651-663
56. Shephard S.E., Zogg M., Burg G., and Panizzon R.G. Measurement of 5-methoxypsoralen and 8-methoxypsoralen in saliva of PUVA patients as a noninvasive, clinically relevant alternative to monitoring in blood. Arch. Dermatol. Red. 291 (1999) 491-499
57. Shimada T., Oda Y., Gillam E.M., Guengerich F.P., and Inoue K. Metabolic activation of polycyclic aromatic hydrocarbons and other procarcinogens by cytochromes P450 1A1 and P450 1B1 allelic variants and other human cytochromes P450 in Salmonella typhimurium NM2009. Drug Metab. Dispos. 29 (2001) 1176-1182
58. Silverman R.B. Mechanism-based enzyme inactivators. In: Purich D.L. (Ed). Contemporary Enzyme Kinetics and Mechanism (1996), Academic Press, San Diego
59. Surh Y.J. Cancer chemoprevention with dietary phytochemicals. Nat. Rev. Cancer 3 (2003) 768-780
60. Talalay P., and Fahey J. Phytochemicals from cruciferous plants protect against cancer by modulating carcinogen metabolism. J. Nutr. 131 (2001) 3027S-3033S
61. Tantcheva-Poor I., Servera-Llaneras M., Scharffetter-Kochanek K., and Fuhr U. Liver cytochrome P450 CYP1A2 is markedly inhibited by systemic but not by bath PUVA in dermatological patients. Br. J. Dermatol. 144 (2001) 1127-1132
62. Teel R.W., and Huynh H. Modulation by phytochemicals of cytochrome P450-linked enzyme activity. Cancer Lett. 133 (1998) 135-141
63. Tucker G.T., Rostami-Hodjegan A., and Jackson P.R. Determination of drug-metabolizing enzyme activity in vivo: pharmacokinetic and statistical issues. Xenobiotica 28 (1998) 1255-1273
64. von Moltke L.L., Weemhoff J.L., Bedir E., Khan I.A., Harmatz J.S., Goldman P., and Greenblatt D.J. Inhibition of human cytochromes P450 by components of Ginkgo biloba. J. Pharm. Pharmacol. 56 (2004) 1039-1044
65. Wagstaff D.J. Dietary exposure to furocoumarins. Regul. Toxicol. Pharmacol. 14 (1991) 261-272
66. Wang J.S., Shen X., He X., Zhu Y.R., Zhang B.C., Wang J.B., Qian G.S., Kuang S.Y., Zarba A., Egner P.A., Jacobson L.P., Munoz A., Helzlsouer K.J., Groopman J.D., and Kensler T.W. Protective alterations in phase 1 and 2 metabolism of aflatoxin B1 by oltipraz in residents of Qidong, People's Republic of China. J. Natl. Cancer Inst. 91 (1999) 347-354
67. Welfare M.R., Bassendine M.F., and Daly A.K. The effect of NAT2 genotype and gender on the metabolism of caffeine in nonsmoking subjects. Br. J. Clin. Pharmacol. 49 (2000) 240-243
68. Yamazaki H., Inui Y.S.A.W., Guengerich F.P., and Shimada T. Procarcinogen activation by cytochrome P450 3A4 and 3A5 expressed in Escherichia coli and by human liver microsomes. Carcinogenesis 16 (1995) 2167-2170
69. Yeo U.-C., Shin J.-H., Yang J.-M., Park K.-B., Kim M.-M., Bok H.-S., and Lee E.-S. Psoralen-ultraviolet A-induced erythema: sensitivity correlates with the concentrations of psoralen in suction blister fluid. Br. J. Dermatol. 142 (2000) 733-739
70. Yiannikouris A., Poughon L., Cameleyre X., Dussap C., François J., Bertin G., and Jouany J. A novel technique to evaluate interactions between Saccharomyces cerevisiae cell wall and mycotoxins: application to zearalenone. Biotechnol. Lett. 25 (2003) 783-789
71. Zhang W., Kilicarslan T., Tyndale R.F., and Sellers E.M. Evaluation of methoxsalen, tranylcypromine, and tryptamine as specific and selective CYP2A6 inhibitors in vitro. Drug Metab. Dispos. 29 (2001) 897-902
72. Zhou S., Koh H.L., Gao Y., Gong Z.Y., and Lee E.J. Herbal bioactivation: the good, the bad and the ugly. Life Sci. 74 (2004) 935-968
73. Zucchi A., Raho E., Marconi B., Nicoli S., Santini M., Allegra F., Colombo P., Bettini R., and Santi P. Plasma and skin concentration of 5-methoxypsoralen in psoriatic patients after oral administration. J. Invest. Dermatol. 117 (2001) 379-382