A rat colon cancer model induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, PhIP

Nakagama, Hitoshi; Ochiai, Masako; Ubagai, Tsuneyuki; Tajima, Rie; Fujiwara, Kyoko; Sügimura, Takashi; Nagao, Minako

doi:10.1016/s0027-5107(02)00160-4

Cited by 40 publications

(23 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Known for their potent mutagenic response on the Ames/Salmonella test (Ames et al 1975) and in Chinese hamster ovary cells (Wu et al 1997), HAA also have been linked to cancer in laboratory rodents and primates (Gold et al 1994;Snyderwine et al 1997;Nagao et al 2002;Nakagama et al 2002). The U.S. Department of Health and Human Services recently listed three HAA, MeIQ, MeIQx, and PhIP, as "reasonably anticipated to be human carcinogens" based on a body of evidence from in vivo studies and human epidemiological data (NIEHS 2005).…”

Section: Introductionmentioning

confidence: 99%

Heterocyclic aromatic amines in domestically prepared chicken and fish from Singapore Chinese households

Salmon

Knize

Felton

et al. 2006

Food and Chemical Toxicology

View full text Add to dashboard Cite

Abstract--Chicken and fish samples prepared by 42 Singapore Chinese in their homes were obtained. Researchers were present to collect data on raw meat weight, cooking time, maximum cooking surface temperature, and cooked meat weight. Each participant prepared one pan-fried fish sample and two pan-fried chicken samples, one marinated, one not marinated. The cooked samples were analyzed for five heterocyclic aromatic amine (HAA) mutagens, including MeIQx Interestingly, the maximum cooking surface temperature was higher for fish than for either marinated or non-marinated chicken (P<0.001), yet fish was lower in 4,8-DiMeIQx per gram than marinated or non-marinated chicken (p<0.001), lower in PhIP than non-marinated chicken (P<0.05), and lost less weight due to cooking than either marinated or non-marinated chicken (P<0.001). Fish was also lower in MeIQx and 7,8-DiMeIQx than marinated chicken (P<0.05).This study provides new information on HAA content in the Singapore Chinese diet.

show abstract

Section: Introductionmentioning

confidence: 99%

Heterocyclic aromatic amines in domestically prepared chicken and fish from Singapore Chinese households

Salmon

Knize

Felton

et al. 2006

Food and Chemical Toxicology

View full text Add to dashboard Cite

show abstract

“…PhIP is a colon (9) and mammary (10,11) carcinogen in rats. Although PhIP is less mutagenic than many other HAAs in bacterial assays (12,13), its relative abundance in food may make PhIP a major contributor to diet-related human cancer (14,15), including breast cancer (16).…”

Section: Introductionmentioning

confidence: 99%

Hplc/Electrospray Ionization Mass Spectrometric Analysis of the Heterocyclic Aromatic Amine Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in Human Milk

Scott

Turesky

Wainman

et al. 2006

Chem. Res. Toxicol.

View full text Add to dashboard Cite

A new procedure has been developed for the extraction of 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) and other heterocyclic aromatic amines from human breast milk samples. Extracts were analyzed by high-performance liquid chromatography/electrospray ionization/tandem mass spectrometry (HPLC/ESI-MS/MS) with selective reaction monitoring detection. Tandem ESI-MS/MS detection provides much improved sensitivity and specificity, compared with those of a previous method that used selected ion monitoring. Milk samples were collected from 48 healthy volunteers, including five vegetarians. Donors completed a detailed dietary questionnaire. The concentrations of PhIP in the milk samples were low and below the limit of quantification (0.68 pg/mL) for all subjects except one, for whom a concentration of 1.0 pg PhIP/mL was measured. Our results indicate that the levels of PhIP in human milk are substantially lower than what was previously reported.

show abstract

“…A rat colon cancer model induced by PhIP shows profiles of cancer development similar to the multistep model of colon carcinogenesis in humans (35). In this rat model, p53 and K-ras mutations are rarely observed, whereas mutations in Apc and its downstream gene ␤-catenin have been frequently observed (21, 36 -38).…”

Section: Discussionmentioning

confidence: 91%

Translesional DNA Synthesis through a C8-Guanyl Adduct of 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in Vitro

Fukuda

Takamura-Enya

Masuda

et al. 2009

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)is the most abundant heterocyclic amine in cooked foods, and is both mutagenic and carcinogenic. It has been suspected that the carcinogenicity of PhIP is derived from its ability to form DNA adducts, principally dG-C8-PhIP. To shed further light on the molecular mechanisms underlying the induction of mutations by PhIP, in vitro DNA synthesis analyses were carried out using a dG-C8-PhIP-modified oligonucleotide template. In this template, the dG-C8-PhIP adduct was introduced into the second G of the TCC GGG AAC sequence located in the 5 region. This represents one of the mutation hot spots in the rat Apc gene that is targeted by PhIP. Guanine deletions at this site in the Apc gene have been found to be preferentially induced by PhIP in rat colon tumors. DNA synthesis with A-or B-family DNA polymerases, such as Escherichia coli polymerase (pol) I and human pol ␦, was completely blocked at the adducted guanine base. Translesional synthesis polymerases of the Y-family, pol , pol , pol , and REV1, were also used for in vitro DNA synthesis analyses with the same templates. REV1, pol , and pol were able to insert dCTP opposite dG-C8-PhIP, although the efficiencies for pol and pol were low. pol was also able to catalyze the extension reaction from the dC opposite dG-C8-PhIP, during which it often skipped over one dG of the triple dG sequence on the template. This slippage probably leads to the single dG base deletion in colon tumors.

show abstract

A rat colon cancer model induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, PhIP

Cited by 40 publications

References 22 publications

Heterocyclic aromatic amines in domestically prepared chicken and fish from Singapore Chinese households

Heterocyclic aromatic amines in domestically prepared chicken and fish from Singapore Chinese households

Hplc/Electrospray Ionization Mass Spectrometric Analysis of the Heterocyclic Aromatic Amine Carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in Human Milk

Translesional DNA Synthesis through a C8-Guanyl Adduct of 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in Vitro

Contact Info

Product

Resources

About