Adduct detection by acylation with [35S]methionine:analysis of DNA adducts of 4-aminobiphenyl.

Sheabar, Fayad Z.; Morningstar, Marshall L.; Wogan, Gerald N.

doi:10.1073/pnas.91.5.1696

Cited by 7 publications

(4 citation statements)

References 19 publications

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“…Epidemiological studies of the hazards to workers in the chemical industry established that benzidine and 2-naphthylamine are carcinogenic to humans (36,124). It was shown that rubber workers also had an increased risk for bladder cancer, attributed largely to exposure to aromatic amines (198).…”

Section: Carcinogen Metabolism During Schistosomiasismentioning

confidence: 99%

Relationship between Schistosomiasis and Bladder Cancer

1999

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SUMMARY Carcinoma of the urinary bladder is the most common malignancy in the Middle East and parts of Africa where schistosomiasis is a widespread problem. Much evidence supports the association between schistosomiasis and bladder cancer: this includes the geographical correlation between the two conditions, the distinctive patterns of gender and age at diagnosis, the clinicopathological identity of schistosome-associated bladder cancer, and extensive evidence in experimentally infected animals. Multiple factors have been suggested as causative agents in schistosome-associated bladder carcinogenesis. Of these, N-nitroso compounds appear to be of particular importance since they were found at high levels in the urine of patients with schistosomiasis-associated bladder cancer. Various strains of bacteria that can mediate nitrosation reactions leading to the formation of N-nitrosamines have been identified in the urine of subjects with schistosomiasis at higher intensities of infection than in normal subjects. In experimental schistosomiasis, the activities of carcinogen-metabolizing enzymes are increased soon after infection but are reduced again during the later chronic stages of the disease. Not only could this prolong the period of exposure to activated N-nitrosamines, but also inflammatory cells, sitmulated as a result of the infection, may induce the endogenous synthesis of N-nitrosamines as well as generating oxygen radicals. Higher than normal levels of host cell DNA damage are therefore anticipated, and they have indeed been observed in the case of alkylation damage, together with an inefficiency in the capacity of relevant enzymes to repair this damaged DNA. In experimental schistosomiasis, it was also found that endogenous levels of host cell DNA damage were related to the intensity of infection. All of these factors could contribute to an increased risk of bladder cancer in patients with schistosomiasis, and in particular, the gene changes observed may have potential for use as biomarkers in the early detection of bladder cancer that may assist in alleviating the problem.

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Section: Carcinogen Metabolism During Schistosomiasismentioning

confidence: 99%

Relationship between Schistosomiasis and Bladder Cancer

1999

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“…To facilitate progress in evaluation of DNA adduct measurements as biomarkers of genotoxic exposure, we have developed a new analytical procedure based on the peracylation of nucleoside adducts with a radiolabeled methionine derivative, (ieri-butoxycarbonyl)-L-[35S]methionine -hydroxysuccinimidyl ester ([35S]TBM-NHS)1 (also known as [35S]sulphur labeling reagent, 35SLR) (9). Peracylation with an activated BOC-methionine derivative appeared to be a facile method of attaching a radiolabel to modified nucleosides, based on several lines * To whom correspondence should be addressed.…”

Section: Introductionmentioning

confidence: 99%

Peracylation of Nucleosides with Methionine: Foundation for a Method To Detect Carcinogen Adducts

Sheabar

Morningstar²,

Wogan³

1994

Chem. Res. Toxicol.

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We report the chemical foundation for a new method to detect carcinogen-DNA adducts, which we have designated adduct detection by acylation with methionine (ADAM). The method is based on reaction of DNA adducts with a protected methionine derivative, (tert-butoxycarbonyl)-L-methionine N-hydroxysuccinimidyl ester (TMB-NHS). Acylation of 2'-deoxyguanosine (dGuo), used as a prototypical deoxynucleoside, and N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dGuo-8-ABP), the major DNA adduct formed after in vivo exposure to 4-aminobiphenyl, a known human carcinogen, with TBM-NHS was optimized, and products were characterized by 3H radioactivity, UV absorbance, mass spectrometry, and 1H and 13C NMR. Derivatives acylated on hydroxyl (5' or 3') and/or amine (N2) groups were unambiguously determined to be mono-, bis-, and tris-TBM-acylated nucleosides. Under optimal acylation conditions [TBM-NHS (> or = 4 x 10(5) molar equivalents), pyridine (50 microL), THF (50 microL), and diisopropylcarbodiimide (DIC) (1 microL) and incubation for 2 h at 37 degrees C], the efficiency of acylation for picomole or smaller quantities of dGuo-8-ABP exceeded 95%, with the tris-TMB-acylated nucleoside representing the major product (88%). A linear correlation was obtained between the amount of [3H]dGuo-8-ABP introduced into the reaction and the total amount of TBM-acylated products formed. These results support the validity of this strategy for adaptation as an analytical method for the detection of low levels of DNA adducts through the use of (tert-butoxycarbonyl)-L-[35S]-methionine N-hydroxysuccinimidyl ester.

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“…When AF stage cells are transplanted, the resultant tumors have lost the receptor modulatory activity, indicative of a functional role in progression. A second characteristic that defines the end-stage tumors is specific genetic changes: in this case, duplications of chromosome 8 and/or loss of portions of chromosome 14 (10).…”

mentioning

confidence: 99%

“…Unfortunately, none of the available analytical methods for carcinogen-DNA adduct measurement provide reliable quantitative data of this type. To address this and other deficiencies in the existing methodology for DNA adduct analysis, we have recently developed an analytical procedure combining advantages of sensitivity, specificity, and relative technical facility (14,15). The procedure involves adduct detection by acylation with methionine (ADAM).…”

mentioning

confidence: 99%

Mechanisms of Toxicity and Carcinogenesis

Trump¹

1995

Toxicol Pathol

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celebrated its Tenth Anniversary this year. Over the course of this decade, these conferences have attracted scientists from varied backgrounds and levels of education and experience, ranging from students and young investigators to prominent senior investigators. Scientists are invited to give presentations which are followed by indepth discussions and then later, informal discussions and gatherings. It is this mix that has provided a decade of extraordinary conferences (for Programs and Abstracts, see Toxicol Pathol Volumes [16][17][18][19][20][21][22][23][1988][1989][1990][1991][1992][1993][1994][1995].The theme of the Aspen Cancer Conference, as originally conceived by Drs. Benjamin F. Trump and Curtis C. Harris, has remained the same: the molecular aspects of toxicity and carcinogenesis and the relationship between the two as they relate to human risk. A two-year cycle was established for the Conference with a smaller Workshop to discuss topics of current timely interest and their relevance of importance followed by recommendations for their consideration in the next year's larger Conference. This cycle brought about a unique approach to such a meeting and has worked extremely well to foster the development and exchange of ideas between scientists from industry, academia, government, and private companies. Over the years, topics discussed have included mitosis and genetic instability; cell division, cell differentiation, and cell death; DNA replication and repair; tumor suppression and oncogenes; oxyradicals; control of the cell cycle; cancer therapy; molecular epidemiology, etc to name but a few. Next year's Eleventh Aspen Cancer Conference Workshop, to be held July 14-16, 1996, will include sessions on Mechanistic Paradigms of Risk Assessment; Carcinogen Assessment Strategies; Oxidants and Antioxidants in Carcinogenesis; Significance of Stem Cells; Status of Molecular Diagnosis; Tumor Progression and Metastasis; Cell Death; Signal Transduction; Gene Therapy; and Endogenous Carcinogens.To celebrate this year's Tenth Anniversary of the Aspen Cancer Conference, an evening session was held in conjunction with the Aspen MD/PhD Student Conference at the Given Biomedical Institute. It consisted of an overview of the Conference's inception, recognition of Dr. Donald West King, and presentation of awards to Drs. King, Trump, and Harris. This was followed by the introduction of last year's Keynote Lecturer, Dr. J. Michael Bishop, who introduced and presented an award to Dr.

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Adduct detection by acylation with [35S]methionine:analysis of DNA adducts of 4-aminobiphenyl.

Cited by 7 publications

References 19 publications

Relationship between Schistosomiasis and Bladder Cancer

Relationship between Schistosomiasis and Bladder Cancer

Peracylation of Nucleosides with Methionine: Foundation for a Method To Detect Carcinogen Adducts

Mechanisms of Toxicity and Carcinogenesis

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