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Promutagenic etheno (epsilon) adducts in DNA are generated through reactions of DNA bases with LPO products derived from endogenous sources or from exposure to several xenobiotics. The availability of sensitive methods has made it possible to detect three epsilon-adducts in vivo, namely epsilon dA, epsilon dC and N2,3-epsilon dG. One probable endogenous(More)
Lipid peroxidation generates reactive aldehydes such as trans-4-hydroxy-2-nonenal and malonaldehyde, which form promutagenic exocyclic DNA adducts in human cells and may contribute to diet-related cancers. Using ultrasensitive detection methods, analysis of WBC DNA from volunteers in a dietary study revealed that high intake of omega-6 polyunsaturated fatty(More)
Nonsteroidal anti-inflammatory drugs (NSAIDs) can regress adenomas in patients with familial adenomatous polyposis (FAP), and the mechanism involves inhibition of cyclooxygenases (COX). Reactive intermediates formed during the arachidonic acid cascade, notably by COX-2, which is upregulated in polyps of FAP patients, may promote various stages of the polyp(More)
Lipid peroxidation generates reactive aldehydes such as trans-4-hydroxy-2-nonenal and malonaldehyde, which form promutagemc exocyclic DNA adducts in human cells and may contribute to diet-related cancers. Using ultrasensitive detection methods, analysis of WBC DNA from volunteers in a dietary study revealed that high intake of w-6 polyunsaturated fatty(More)
Etheno adducts in DNA are formed from the carcinogens vinyl chloride and urethane, and also from products of lipid peroxidation (LPO), such as trans-4-hydroxy-2-nonenal. Using an ultrasensitive detection method, the formation of etheno-DNA adducts in the liver was demonstrated in LEC rats (a strain with hereditary abnormal copper metabolism) that develop(More)
DNA adducts associated with oxidative stress are believed to involve the formation of endogenous reactive species generated by oxidative damage and lipid peroxidation. Although these adducts have been reported in several human tissues by different laboratories, a comparison of the levels of these adducts in the same tissue samples has not been carried out.(More)
[7-3H]Styrene 7,8-oxide was administered by oral gavage to male CD rats at a dose of 1.3 mg/kg. After 4 h, the forestomach was excised, DNA was isolated, purified to constant specific radioactivity and degraded enzymatically to the 3'-nucleotides. High-performance liquid chromatography fractions with the normal nucleotides contained most of the radiolabel,(More)
The effect of cell replication on histone-carcinogen adducts was investigated by determining the specific adduct levels as a function of time following carcinogen treatment of human TK6 cells grown in culture. Core histones isolated from cells treated with aflatoxin B1 or r-7,t-8 dihydroxy-t-9,t-10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene exhibited a(More)
It is increasingly recognised that DNA (and other cellular) damage from endogenous processes and agents could play a major role in the aetiology of several human cancers and of (neuro)degenerative diseases. Understanding the underlying molecular mechanisms would offer new approaches to preventive and therapeutic measures. A workshop on DNA damage from(More)
The effect of cell replication on hlstone-cardnogen adducts was inves tigated by determining the specific adduct levels as a function of time following carcinogen treatment of human TK6 cells grown in culture Core histones Isolated from cells treated with aflatOXIn B1 or r-7,t-8 dihydroxy-t.9,t-1O-epoxy-7,8,9,1O-tetrahydrobenzo[a]pyrene exhibited a decrease(More)