Skip Navigation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (273)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Felton, J.S.
Right arrow Articles by Hatch, F.T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Felton, J.S.
Right arrow Articles by Hatch, F.T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 1986 Oxford University Press

research-article

The isolation and identification of a new mutagen from fried ground beef: 2-amino-l-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP)

J.S. Felton, M.G. Knize, N.H. Shen, P.R. Lewis, B.D. Andresen, J. Happe and F.T. Hatch

Biomedical and Environmental Research Program, Lawrence Livermore National Laboratory, University of California L-452, PO Box 5507, Livermore, CA 94550, USA

A new mutagenic compound has been isolated from ground beef which was fried at 300°C for 5.5 min on each side. The new mutagen was purified using an aqueous acid extraction, XAD-2 adsorption-solvent elution, a series of preparative and analytical h.p.l.c. purification steps, and monitored with the Ames/Salmonella assay. This study reveals a new mutagen member of the amino-imidazoazaarene class of aromatic amines, having a mol. w of 224, and a formula of C13H12N4 as determined by high-resolution mass spectrometry. N.m.r. spectrometry supports the structure, 2-amino-l-methyl-6-phenyl-imidazo[4, 5-b]pyridine (PhIP), for the new mutagen. The 1-methyl and 3-methyl synthesized isomers of PhIP were compared to the purified mutagen. The two isomers had identical mass spectra to the purified compound, but only the 1-methyl isomer showed similar u.v. and n.m.r. spectra. The two synthetic isomers were separable by h.p.l.c. and the beef derived component co-eluted with the 1-methyl-PhIP isomer. PhIP has a specific activity in the Ames/Salmonella assay of 1950 revertants/µg. Although it is not as mutagenic as other compounds isolated from fried beef (e.g. MelQx, 58 000 revertants/µg) it is the most abundant mutagenic compound by mass in fried beef. PhIP is present at approximately 15 p.p.b. of the original weight of uncooked beef (accounting for 75% of the mass of genotoxic material) and contributes 18% of the total mutagenicity of the fried beef.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
H. Fukuda, T. Takamura-Enya, Y. Masuda, T. Nohmi, C. Seki, K. Kamiya, T. Sugimura, C. Masutani, F. Hanaoka, and H. Nakagama
Translesional DNA Synthesis through a C8-Guanyl Adduct of 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in Vitro: REV1 INSERTS dC OPPOSITE THE LESION, AND DNA POLYMERASE {kappa} POTENTIALLY CATALYZES EXTENSION REACTION FROM THE 3'-dC TERMINUS
J. Biol. Chem., September 18, 2009; 284(38): 25585 - 25592.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
R. W. Dellinger, G. Chen, A. S. Blevins-Primeau, J. Krzeminski, S. Amin, and P. Lazarus
Glucuronidation of PhIP and N-OH-PhIP by UDP-glucuronosyltransferase 1A10
Carcinogenesis, November 1, 2007; 28(11): 2412 - 2418.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. N. Lauber and N. J. Gooderham
The Cooked Meat Derived Genotoxic Carcinogen 2-Amino-3-Methylimidazo[4,5-b]Pyridine Has Potent Hormone-Like Activity: Mechanistic Support for a Role in Breast Cancer
Cancer Res., October 1, 2007; 67(19): 9597 - 9602.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
D. Tang, J. J. Liu, A. Rundle, C. Neslund-Dudas, A. T. Savera, C. H. Bock, N. L. Nock, J. J. Yang, and B. A. Rybicki
Grilled Meat Consumption and PhIP-DNA Adducts in Prostate Carcinogenesis
Cancer Epidemiol. Biomarkers Prev., April 1, 2007; 16(4): 803 - 808.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
J. S. Felton and M. G. Knize
A meat and potato war: implications for cancer etiology
Carcinogenesis, December 1, 2006; 27(12): 2367 - 2370.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. A. Malfatti, K. H. Dingley, S. Nowell-Kadlubar, E. A. Ubick, N. Mulakken, D. Nelson, N. P. Lang, J. S. Felton, and K. W. Turteltaub
The Urinary Metabolite Profile of the Dietary Carcinogen 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]Pyridine Is Predictive of Colon DNA Adducts after a Low-Dose Exposure in Humans
Cancer Res., November 1, 2006; 66(21): 10541 - 10547.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
K. Fujiwara, M. Ochiai, T. Ohta, M. Ohki, H. Aburatani, M. Nagao, T. Sugimura, and H. Nakagama
Global gene expression analysis of rat colon cancers induced by a food-borne carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
Carcinogenesis, August 1, 2004; 25(8): 1495 - 1505.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. E. van Herwaarden, J. W. Jonker, E. Wagenaar, R. F. Brinkhuis, J. H. M. Schellens, J. H. Beijnen, and A. H. Schinkel
The Breast Cancer Resistance Protein (Bcrp1/Abcg2) Restricts Exposure to the Dietary Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
Cancer Res., October 1, 2003; 63(19): 6447 - 6452.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
W.G. Stillwell, R. Sinha, and S.R. Tannenbaum
Excretion of the N2-glucuronide conjugate of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine in urine and its relationship to CYP1A2 and NAT2 activity levels in humans
Carcinogenesis, May 1, 2002; 23(5): 831 - 838.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
M. Futakuchi, M. Hirose, K. Imaida, S. Takahashi, K. Ogawa, M. Asamoto, T. Miki, and T. Shirai
Chemoprevention of 2-amino-1-methyl-6-phenylimidazo- [4,5-b]pyridine-induced colon carcinogenesis by 1-O-hexyl-2,3,5-trimethylhydroquinone after initiation with 1,2-dimethylhydrazine in F344 rats
Carcinogenesis, February 1, 2002; 23(2): 283 - 287.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
T. Ubagai, M. Ochiai, T. Kawamori, H. Imai, T. Sugimura, M. Nagao, and H. Nakagama
Efficient induction of rat large intestinal tumors with a new spectrum of mutations by intermittent administration of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in combination with a high fat diet
Carcinogenesis, January 1, 2002; 23(1): 197 - 200.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
I.-L. Steffensen, H. A. J. Schut, J. E. Paulsen, A. Andreassen, and J. Alexander
Intestinal Tumorigenesis in Multiple Intestinal Neoplasia Mice Induced by the Food Mutagen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine: Perinatal Susceptibility, Regional Variation, and Correlation with DNA Adducts
Cancer Res., December 1, 2001; 61(24): 8689 - 8696.
[Abstract] [Full Text] [PDF]

Home page
 MutagenesisHome page
G. R. Stuart, J. G. de Boer, R. Haesevoets, J. Holcroft, J. Kangas, K. Sojonky, E. Thorleifson, A. Thornton, D. F. Walsh, H. Yang, et al.
Mutations induced by 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) in cecum and proximal and distal colon of lacI transgenic rats
Mutagenesis, September 1, 2001; 16(5): 431 - 437.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
K. Imaida, M. Sano, S. Tamano, M. Asamoto, K. Ogawa, M. Futakuchi, and T. Shirai
Organ dependent enhancement of rat 3,2'-dimethyl-4-aminobiphenyl (DMAB) carcinogenesis by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP): positive effects on the intestine but not the prostate
Carcinogenesis, August 1, 2001; 22(8): 1295 - 1299.
[Abstract] [Full Text] [PDF]

Home page
 MutagenesisHome page
A. Andreassen, R. Vikse, I.-L. Steffensen, J. E. Paulsen, and J. Alexander
Intestinal tumours induced by the food carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in multiple intestinal neoplasia mice have truncation mutations as well as loss of the wild-type Apc+ allele
Mutagenesis, July 1, 2001; 16(4): 309 - 315.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
K. Brown, B. E. Hingerty, E. A. Guenther, V. V. Krishnan, S. Broyde, K. W. Turteltaub, and M. Cosman
Solution structure of the 2-amino-1- methyl-6-phenylimidazo[4,5-b]pyridine C8-deoxyguanosine adduct in duplex DNA
PNAS, June 28, 2001; (2001) 151251898.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
C. G. Dietrich, D.R. de Waart, R. Ottenhoff, A. H. Bootsma, A. H. van Gennip, and R. P.J.O. Elferink
Mrp2-deficiency in the rat impairs biliary and intestinal excretion and influences metabolism and disposition of the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)
Carcinogenesis, May 1, 2001; 22(5): 805 - 811.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
C. G. Dietrich, D. R. de Waart, R. Ottenhoff, I. G. Schoots, and R. P. J. O. Elferink
Increased Bioavailability of the Food-Derived Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in MRP2-Deficient Rats
Mol. Pharmacol., April 16, 2001; 59(5): 974 - 980.
[Abstract] [Full Text]

Home page
 Drug Metab. Dispos.Home page
D. W. Hein, C. A. McQueen, D. M. Grant, G. H. Goodfellow, F. F. Kadlubar, and W. W. Weber
Pharmacogenetics of the Arylamine N-Acetyltransferases: A Symposium in Honor of Wendell W. Weber
Drug Metab. Dispos., April 13, 2001; 28(12): 1425 - 1432.
[Abstract] [Full Text]

Home page
 CarcinogenesisHome page
J.C. Klein, R.B. Beems, P.E. Zwart, M. Hamzink, G. Zomer, H.v. Steeg, and C.F.v. Kreijl
Intestinal toxicity and carcinogenic potential of the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in DNA repair deficient XPA-/- mice
Carcinogenesis, April 1, 2001; 22(4): 619 - 626.
[Abstract] [Full Text] [PDF]

Home page
 MutagenesisHome page
J. A. Heddle, M. G. Knize, D. Dawod, and X.-B. Zhang
A test of the mutagenicity of cooked meats in vivo
Mutagenesis, March 1, 2001; 16(2): 103 - 107.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
R. Sinha, D. R. Gustafson, M. Kulldorff, W.-Q. Wen, J. R. Cerhan, and W. Zheng
2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, a Carcinogen in High- Temperature-Cooked Meat, and Breast Cancer Risk
J Natl Cancer Inst, August 16, 2000; 92(16): 1352 - 1354.
[Full Text] [PDF]

Home page
 CarcinogenesisHome page
T. Ohta, S. Nakatsugi, K. Watanabe, T. Kawamori, F. Ishikawa, M. Morotomi, S. Sugie, T. Toda, T. Sugimura, and K. Wakabayashi
Inhibitory effects of Bifidobacterium-fermented soy milk on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced rat mammary carcinogenesis, with a partial contribution of its component isoflavones
Carcinogenesis, May 1, 2000; 21(5): 937 - 941.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
G. R. Stuart, J. Holcroft, J. G. de Boer, and B. W. Glickman
Prostate Mutations in Rats Induced by the Suspected Human Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
Cancer Res., January 1, 2000; 60(2): 266 - 268.
[Abstract] [Full Text]

Home page
 Toxicol PatholHome page
Y. Ikeda, S. Takahashi, J. Kimura, Y.-M. Cho, K. Imaida, S. Shirai, and T. Shirai
Anophthalmia in Litters of Female Rats Treated with the Food-Derived Carcinogen, 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]Pyridine
Toxicol Pathol, November 1, 1999; 27(6): 628 - 631.
[Abstract] [PDF]

Home page
 CarcinogenesisHome page
J. E. Paulsen, I.-L. Steffensen, A. Andreassen, R. Vikse, and J. Alexander
Neonatal exposure to the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine via breast milk or directly induces intestinal tumors in multiple intestinal neoplasia mice
Carcinogenesis, July 1, 1999; 20(7): 1277 - 1282.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
M. Venugopal, A. Callaway, and E. G. Snyderwine
2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) retards mammary gland involution in lactating Sprague–Dawley rats
Carcinogenesis, July 1, 1999; 20(7): 1309 - 1314.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
Y. Ishiguro, M. Ochiai, T. Sugimura, M. Nagao, and H. Nakagama
Strain differences of rats in the susceptibility to aberrant crypt foci formation by 2-amino-1-methyl-6-phenylimidazo- [4,5-b]pyridine: no implication of Apc and Pla2g2a genetic polymorphisms in differential susceptibility
Carcinogenesis, June 1, 1999; 20(6): 1063 - 1068.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
S. A. Nowell, J. S. Massengill, S. Williams, A. Radominska-Pandya, T. R. Tephly, Z. Cheng, C. P. Strassburg, R. H. Tukey, S. L. MacLeod, N. P. Lang, et al.
Glucuronidation of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine by human microsomal UDP-glucuronosyltransferases: identification of specific UGT1A family isoforms involved
Carcinogenesis, June 1, 1999; 20(6): 1107 - 1114.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
M. A. Malfatti, K. S. Kulp, M. G. Knize, C. Davis, J. P. Massengill, S. Williams, S. Nowell, S. MacLeod, K. H. Dingley, K. W. Turteltaub, et al.
The identification of [2-14C]2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine metabolites in humans
Carcinogenesis, April 1, 1999; 20(4): 705 - 713.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
T Sugimura
Multistep carcinogenesis: a 1992 perspective
Science, October 23, 1992; 258(5082): 603 - 607.
[Abstract] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
K. Brown, B. E. Hingerty, E. A. Guenther, V. V. Krishnan, S. Broyde, K. W. Turteltaub, and M. Cosman
Solution structure of the 2-amino-1- methyl-6-phenylimidazo[4,5-b]pyridine C8-deoxyguanosine adduct in duplex DNA
PNAS, July 17, 2001; 98(15): 8507 - 8512.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.