Detection of Cisplatin—DNA Adducts in Humans

Poirier, Miriam C.; Gupta-Burt, Shalina; Litterst, Charles L.; Reed, Eddie

doi:10.1021/bk-1990-0451.ch027

Cited by 4 publications

(2 citation statements)

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“…Among these biomacromolecules, DNA is a genetic material indicating important biological roles in gene expression, transcription, mutagenesis, and carcinogenesis [31]. Many drugs and toxics compounds reflect their biological and toxically activities through their binding interactions with DNA [32][33][34][35][36][37]. Above these interactions are likely to interfere with enzymes (e.g.…”

Section: Introductionmentioning

confidence: 99%

Exploration of binding of bisphenol A and its analogues with calf thymus DNA by optical spectroscopic and molecular docking methods

Wang

Zhang

2015

Journal of Photochemistry and Photobiology B: Biology

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Section: Introductionmentioning

confidence: 99%

Exploration of binding of bisphenol A and its analogues with calf thymus DNA by optical spectroscopic and molecular docking methods

Wang

Zhang

2015

Journal of Photochemistry and Photobiology B: Biology

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“…Methods that have been used for sensitive detection of carcinogen-DNA adducts in humans include immunoassays (5), immunohistochemistry (6,7), 32p_ postlabeling, (8,9), fluorescence and phosphorescence spectroscopy (10), gas chromatography-mass spectrometry (GC-MS) (11), atomic absorbance spectrometry (AAS) (12,13) and electrochemical conductance (ECC) (14). Typically, the techniques that are used without preparative procedures are not absolutely quantitative or able to chemically characterize a specific adduct, but they are highly effective screening tools.…”

Section: Introductionmentioning

confidence: 99%

Human DNA adduct measurements: state of the art.

Poirier

Weston

1996

Environ Health Perspect

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Human DNA adduct formation (covalent modification of DNA with chemical carcinogens) is a promising biomarker for elucidating the molecular epidemiology of cancer. Classes of compounds for which human DNA adducts have been observed include polycyclic aromatic hydrocarbons (PAHs), nitrosamines, mycotoxins, aromatic amines, heterocyclic amines, ultraviolet light, and alkylating cancer chemotherapeutic agents. Most human DNA adduct exposure monitoring has been performed with either 32P-postlabeling or immunoassays, neither of which is able to chemically characterize specific DNA adducts. Recently developed combinations of methods with chemical and physical end points have allowed identification of specific adducts in human tissues. Studies are presented that demonstrate that high ambient levels of benzo[a]pyrene are associated with high levels of DNA adducts in human blood cell DNA and that the same DNA adduct levels drop when the ambient PAH levels decrease significantly. DNA adduct dosimetry, which has been achieved with some dietary carcinogens and cancer chemotherapeutic agents, is described, as well as studies correlating DNA adducts with other biomarkers. It is likely that some toxic, noncarcinogenic compounds may have genotoxic effects, including oxidative damage, and that adverse health outcomes other than cancer may be correlated with DNA adduct formation. The studies presented here may serve as useful prototypes for exploration of other toxicological end points.

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Structural characterization of carcinogen‐modified oligodeoxynucleotide adducts using matrix‐assisted laser desorption/ionization mass spectrometry

et al. 2002

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The aim of this study was to determine the chemical structure of in vitro 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-modified oligodeoxynucleotides (ODNs) by exonuclease digestion and matrix-assisted laser desorption/ionization mass spectrometry. A single-stranded 11-mer ODN, 5-d(CCATCGCTACC), was reacted with N-acetoxy-PhIP, resulting in the formation of one major and eight minor PhIP-ODN adducts. A 10 min treatment of the major and one minor PhIP-ODN adduct with a 3-exonuclease, bovine intestinal mucosa phosphodiesterase (BIMP), and a 5-exonuclease, bovine spleen phosphodiesterase, results in inhibition of the primary exonuclease activity at deoxyguanosine (dG) producing 5-d(CCATCG(PhIP)) and 5-d(G(PhIP)CTACC) product ions, respectively. Post-source decay (PSD) of these enzymatic end products identifies dG as the sole modification site in two 11-mer ODN-PhIP adducts. PSD of the minor PhIP-ODN adduct digestion end product, 5-d(CCATCG(PhIP)), also reveals that the PhIP adducted guanine moiety is in an oxidized form. Prolonged treatment of the PhIP-ODN adducts at 37 • C with BIMP induces a non-specific, or endonuclease, enzymatic activity culminating in the formation of deoxyguanosine 5-monophosphate-PhIP (5-dGMP-PhIP). The PSD fragmentation pattern of the 5-dGMP-PhIP [M + H] + ion of the major adduct confirms PhIP binds to the C-8 position of dG. For the minor adduct, PSD results suggest that PhIP binds to the C-8 position of an oxidized guanine, supporting the hypothesis that this adduct arises from oxidative degradation, resulting in a spirobisguanidino structure.

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Detection of Cisplatin—DNA Adducts in Humans

Cited by 4 publications

References 0 publications

Exploration of binding of bisphenol A and its analogues with calf thymus DNA by optical spectroscopic and molecular docking methods

Exploration of binding of bisphenol A and its analogues with calf thymus DNA by optical spectroscopic and molecular docking methods

Human DNA adduct measurements: state of the art.

Structural characterization of carcinogen‐modified oligodeoxynucleotide adducts using matrix‐assisted laser desorption/ionization mass spectrometry

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