Formation and analysis of heterocyclic aromatic amine–DNA adducts in vitro and in vivo

Turesky, Robert J.; Vouros, Paul

doi:10.1016/j.jchromb.2003.10.053

Cited by 96 publications

(116 citation statements)

References 85 publications

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“…An alternative, non-invasive source of tissue would be desirable. Buccal mucosa tissue has been successfully used to measure DNA adducts in smokers 130) and exfoliated urothelial cells for compounds that are associated with urinary bladder cancer 131) . White blood cells are another alternative tissue source, but there are doubts as to what extent the DNA adducts in leukocytes reflect DNA adduct formation in target tissues.…”

Section: Dna-adductsmentioning

confidence: 99%

Biological Monitoring of Exposure: Trends and Key Developments

Jakubowski

Trzcinka-Ochocka

2005

Journal of Occupational Health

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In the United States it belongs rather to the field of occupational hygiene. It seems that both the approaches can be accepted. More attention should be paid to the development of the truly health-based biomarkers of exposure based on the dose-effect and dose-response relationships. New areas of application of BM of occupational exposure include determination of DNA and protein adducts, unchanged volatile organic compounds in urine, monitoring of exposure to pesticides, antineoplastic drugs, hard metals, and polycyclic aromatic hydrocarbons. In the general environment BM is the most valuable tool for acquiring knowledge of current levels of internal exposure to xenobiotics, identifying the hot spots and developments in trends of exposure. BM can provide policy makers with more accurate information on the control measures undertaken. At present, the main areas include heavy metals, persistent organic pollutants and pesticides. BM of chemical exposure has become increasingly important in the assessment of the health risk in occupational and environmental medicine. Therefore it would be worthwhile to include BM in the curricula for the training of occupational hygienists. (J Occup Health 2005; 47: 22-48)

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Section: Dna-adductsmentioning

confidence: 99%

Biological Monitoring of Exposure: Trends and Key Developments

Jakubowski

Trzcinka-Ochocka

2005

Journal of Occupational Health

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“…As mentioned earlier, the guanine C 8 -IQ adduct is formed more readily in DNA than the N 2 -IQ adduct, but the N 2 -IQ accumulates in vivo due to slower repair (27,28). IQ is mutagenic in human lymphoblastoid cells, but the limited mutation is probably the result of deficient bioactivation (40).…”

mentioning

confidence: 94%

“…1). Both of these adducts are formed upon reaction of DNA with N-hydroxy IQ (27), but the proportion of the N 2 -IQ adduct increases with time in vivo (in rodents) due to much slower repair (27,28). Both adducts were positioned at both the G 1 and the G 3 sites in the NarI sequence, which are known to be resistant and sensitive, respectively, to frameshift mutations with AAF (19,29).…”

mentioning

confidence: 99%

“…In addition, one concern about much of the earlier work with AAF is the identity of the adducts. Although the C 8 -guanyl adduct is the most plentiful in the treatment of DNA with N-hydroxy-IQ (27) or N-acetoxy-AAF (55,56), some N 2 -guanyl adduct is formed, and oligonucleotides substituted with C 8 -and N 2 -guanyl adducts might not be readily discerned except with careful UV or MS CID analysis. The difference in the course of the primer extensions of the C 8 -and N 2 -IQ G 3 adducts is remarkable (Fig.…”

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confidence: 99%

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Biochemical Basis of Genotoxicity of Heterocyclic Arylamine Food Mutagens

Choi

Stover

Angel

et al. 2006

Journal of Biological Chemistry

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Heterocyclic arylamines are highly mutagenic and cause tumors in animal models. The mutagenicity is attributed to the C 8 -and N 2 -G adducts, the latter of which accumulates due to slower repair. The C 8 -and N 2 -G adducts derived from 2-amino-3-methylimidazo[4,5-f ]quinoline (IQ) were placed at the G 1 and G 3 sites of the NarI sequence, in which the G 3 site is an established hot spot for frameshift mutation with the model arylamine derivative 2-acetylaminofluorene but G 1 is not. Human DNA polymerase (pol) extended primers beyond template G-IQ adducts better than did pol and much better than pol or ␦. In 1-base incorporation studies, pol inserted C and A, pol inserted T, and pol inserted G. Steady-state kinetic parameters were measured for these dNTPs opposite the C 8 -and N 2 -IQ adducts at both sites, being most favorable for pol . Mass spectrometry of pol extension products revealed a single major product in each of four cases; with the G 1 and G 3 C 8 -IQ adducts, incorporation was largely error-free. With the G 3 N 2 -IQ adduct, a ؊2 deletion occurred at the site of the adduct. With the G 1 N 2 -IQ adduct, the product was error-free at the site opposite the base and then stalled. Thus, the pol products yielded frameshifts with the N 2 but not the C 8 IQ adducts. We show a role for pol and the complexity of different chemical adducts of IQ, DNA position, and DNA polymerases.

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“…Numerous methods have been developed for the detection of PhIP-derived DNA adducts, which include 32 P-Postlabelling in combination with thin layer chromatography (TLC) or high performance liquid chromatography [16][17][18][19][20], immunological methods [7,9], gas chromatography-mass spectrometry following alkaline hydrolysis of PhIP adducts to the parent amine [21,22] and accelerator mass spectrometry [23][24][25]. 32 P-Postlabelling has been the most widely used method for the detection of PhIP-DNA adducts in animal and human tissues offering the advantage that only small amounts of DNA are required for analysis.…”

Section: Introductionmentioning

confidence: 99%

Detection and quantitation of N-(deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine adducts in DNA using online column-switching liquid chromatography tandem mass spectrometry

Singh

Arlt

Henderson

et al. 2010

Journal of Chromatography B

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The heterocyclic aromatic amine, 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) is formed by the grilled cooking of certain foods such as meats, poultry and fish. PhIP has been shown to induce tumours in the colon, prostate and mammary glands of rats and is regarded as a potential human dietary carcinogen. PhIP is metabolically activated via cytochrome P450 mediated oxidation to an N-hydroxylamino-PhIP intermediate that is subsequently converted to an ester by N-acetyltransferases or sulfotransferases and undergoes heterolytic cleavage to produce a PhIP-nitrenium ion, which reacts with DNA to form the N-(deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP-C8-dG) adduct. Thus far, the detection and quantification of PhIP-DNA adducts has relied to a large extent on 32 P-postlabelling methodologies. In order to expand the array of available techniques for the detection and improved quantification of PhIP-C8-dG adducts in DNA we have developed an online column-switching liquid chromatography (LC)-electrospray ionization (ESI)-tandem mass spectrometry (MS/MS) selected reaction monitoring (SRM) method incorporating an isotopically [ 13 C 10 ]-labelled PhIP-C8-dG internal standard for the analysis of DNA enzymatically hydrolysed to 2′-deoxynucleosides. A dose-dependent increase was observed for PhIP-C8-dG adducts when salmon testis DNA was reacted with N-acetoxy-PhIP. Analysis of DNA samples isolated from colon tissue of mice treated by oral gavage daily for 5 days with 50 mg/kg body weight of PhIP resulted in the detection of an average level of 14.8 ± 3.7 PhIP-C8-dG adducts per 10 6 2′-deoxynucleosides. The method required 50 μg of hydrolysed animal DNA on column and the limit of detection for PhIP-C8-dG was 2.5 fmol (1.5 PhIP-C8-dG adducts per 10 8 2′-deoxynucleosides). In summary, the LC-ESI-MS/MS SRM method provides for the rapid automation of the sample clean up and a reduction in matrix components that would otherwise interfere with the mass spectrometric analysis, with sufficient sensitivity and precision to analyse DNA adducts in animals exposed to PhIP.

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Formation and analysis of heterocyclic aromatic amine–DNA adducts in vitro and in vivo

Cited by 96 publications

References 85 publications

Biological Monitoring of Exposure: Trends and Key Developments

Biological Monitoring of Exposure: Trends and Key Developments

Biochemical Basis of Genotoxicity of Heterocyclic Arylamine Food Mutagens

Detection and quantitation of N-(deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine adducts in DNA using online column-switching liquid chromatography tandem mass spectrometry

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