DNA and protein adducts

Hemminki, K.; Autrup, Herman; Haugen, Aage

doi:10.1016/0300-483x(95)03015-8

Cited by 25 publications

(25 citation statements)

References 61 publications

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“…This manuscript is included in the appendix. There, we described the method of postlabeling carcinogen-DNA adducts by acetylation with 14 C-acetic anhydride combined with quantitation of 14 C by accelerator mass spectrometry (AMS). For this purpose, adducts of benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide (BPDE) with DNA and deoxyguanosine (dG) were synthesized.…”

Section: Cap For Bpde Adductsmentioning

confidence: 99%

“…CAP for 4ABP adducts: This method also is based on postlabeling the carcinogen-DNA adducts with 14 C-acetic anhydride (Ac 2 0) coupled with accelerator mass spectroscopy (AMS). Briefly the method the method involves digesting the sample DNA to yield a mixture adducted and nonadducted nucleotides.…”

Section: C18 (50mg)mentioning

confidence: 99%

“…Purifying the adducted nucleotides by immunopurification procedure follows this. Subsequently the carcinogen-base adducts are subjected to an acylation procedure using 14 C-acetic anhydride. The products are isolated using HPLC followed by detection using AMS procedure.…”

Section: C18 (50mg)mentioning

confidence: 99%

“…Once the profiles the compounds have been set, scale down the amount of starting material (4-ABP) and the amount acetic anhydride. Subsequently go in for standardizing using 14 C labeled acetic anhydride. Validate the ability of 4-ABP to bind to antibodies generated against ABP-Gu adducts.…”

Section: C18 (50mg)mentioning

confidence: 99%

“…We are attempting to establish a new assay for the detection of carcinogen-DNA adducts, use it for the first time in humans, and rigorously validate it to prove its utility for human breast tissue analysis in epidemiological studies. This assay is novel because it uses a new chemical postlabeling method and quantitates adducts by accelerator mass spectroscopy (an ultrasensitive 14 C detection unit). We will develop and rigorously validate the assays using benzo(a)pyrene-(BPDE) and 4-aminobiphenyl (4-ABP)-related adducts as prototypes.…”

Section: (4) Introductionmentioning

confidence: 99%

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Molecular Epidemiology of Breast Cancer: Development and Validation of Acetylation Methods for Carcinogen-DNA Adduct Detection

Shields¹

2002

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and Molecular epidemiology can elucidate new breast cancer risk factors and gene-environment interactions relating to both hormonal and non-hormonal carcinogenic mechanisms. Corroborative epidemiological studies of intermediate biomarkers of carcinogenesis and laboratory studies demonstrating functional importance of the epidemiology findings are needed. The study of carcinogen-DNA adducts can provide corroborative evidence for the importance of genetic susceptibilities in breast cancer risk. We are establishing new assays for the detection of carcinogen-DNA adducts, use it for the first time in humans, and rigorously validate it to prove its utility for human breast tissue analysis in epidemiological studies, and determine adduct levels in relation to metabolizing gene polymorphisms. The assays are novel because one uses a new chemical postlabeling method and quantitates adducts by accelerator mass spectroscopy (an ultrasensitive ,4 C detection unit). The second uses capillary HPLC and laser-induced flourescence. Once validated, we will learn the variability for DNA adduct levels in the population as it relates to age, gender, race, and smoking in breast tissues from 235 donors (200 women, 35 men). We also will develop breast strains from normal donors, determine in vitro adduct formation levels and correlate these levels with p53 induction. Thus, this study will provide new information about genotype-phenotype relationships.14. SUBJECT Currently, many ongoing breast cancer studies are exploring risks related to genetic polymorphisms in these genes. Yet these studies by themselves do not provide absolute proof of etiology or causality. Thus, corroborative epidemiological studies of intermediate biomarkers of carcinogenesis and laboratory studies demonstrating functional importance of the epidemiology findings are needed. We are focusing on carcinogen-DNA adducts because they are promutagenic and lead to alterations in cancer susceptibility genes. They also serve as a marker of the biologically effective dose of a carcinogen, indicating a person's phenotype for metabolism, DNA repair and apoptosis. Several available carcinogen DNA-adduct assays might be useful here, but they are not sufficiently specific and/or sensitive for testing mechanistic hypotheses in humans. We are attempting to establish a new assay for the detection of carcinogen-DNA adducts, use it for the first time in humans, and rigorously validate it to prove it...

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Section: Cap For Bpde Adductsmentioning

confidence: 99%

Section: C18 (50mg)mentioning

confidence: 99%

Section: C18 (50mg)mentioning

confidence: 99%

Section: C18 (50mg)mentioning

confidence: 99%

Section: (4) Introductionmentioning

confidence: 99%

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