Crotonaldehyde is a representative alpha,beta-unsaturated aldehyde endowed of mutagenic and carcinogenic properties related to its propensity to react with DNA. Cyclic crotonaldehyde-derived deoxyguanosine (CrA-PdG) adducts can undergo ring opening in duplex DNA to yield a highly reactive aldehydic moiety. Here, we demonstrate that site-specifically modified DNA oligonucleotides containing a si...

The levels of aromatic/hydrophobic DNA adducts were analyzed in normal lung tissue from 63 lung cancer patients and examined in relation to exposure and genetic factors. Adduct levels were significantly higher in smokers than in nonsmokers, but among smokers the number of cigarettes smoked per day had only low significance for the variation in adduct levels. An inverse correlation was found bet...

The reaction of 2,3-anti-2-tert-butyldimethylsiloxy-3-substituted butanal derivative [anti-B, (±)-10 and (±)-16] derived from trans-(2,3)-epoxy butanoate (1) with carbon nucleophiles [α-furyl anion, acetate anion, and indium (In)-assisted allyl anion] has been investigated to give selectively the anti-, anti-adduct D. This anti-stereoselection could be explained by the Felkin-Anh transition sta...

Genetic polymorphisms in genes involved in processes that affect DNA damage may explain part of the large interindividual variation in DNA adduct levels in smokers. We investigated the effect of 19 polymorphisms in 12 genes involved in carcinogen metabolism, DNA repair, and oxidant metabolism on DNA adduct levels (determined by (32)P post-labeling) in lymphocytes of 63 healthy Caucasian smokers...

Certain aromatic amines carcinogenic for the human urinary bladder, such as 4-aminobiphenyl, undergo hepatic metabolic activation to N-hydroxylamines, which are transported to the bladder. During the transport process, these reactive species come in contact with hemoglobin and react with this blood protein. The principal hemoglobin adduct formed is a cysteine sulfinamide, and quantitative metho...

Exposure of human blood plasma to peroxynitrite in the presence of 3,5-dibromo-4-nitrosobenzenesulphonic acid (DBNBS) resulted in the trapping of a strongly immobilized nitroxide radical adduct. The adduct was due to protein-centred radicals derived not only from serum albumin but also from other major plasma proteins (fibrinogen, IgG, alpha1-antitrypsin and transferrin). Urate significantly pr...

Correlations among biomarkers, an important issue in biomarker research, provide enhanced insight and understanding of the complexity of molecular mechanisms initiated by environmental genotoxic agents in the human organism. Occupational and environmental exposures mostly represent mixtures of genotoxic agents, whereas the specificity of biomarker measurements varies widely. Here, we give an ov...

The intensities of immunofluorescence in nuclei stained by an antiserum specific for the DNA adduct N-deoxyguanosin(8-yl)aminofluorene (dG-8-AF), were quantified by microfluorometry in frozen liver sections from male Fischer rats fed 2-acetylaminofluorene (AAF). Results of previous studies demonstrated that dG-8-AF is the predominant adduct (80-100%) formed in livers of rats fed AAF continuousl...

The persistence of benzo(a)pyrene (BP) metabolite:DNA adducts has been studied in lung and liver of A/HeJ and C57BL/6J mice after a dose of BP (6 mg/mouse) which induces pulmonary adenomas in A/HeJ mice but not in C57BL/6J mice. BP is not a hepatic carcinogen in either strain. Following p.o. administration of [3H]BP, animals were killed at times ranging from 10 hr to 28 days, and BP metabolite:...

In an attempt to elucidate the relationship between DNA adduct formation and tumorigenesis, DNA adducts were measured in the livers and bladders of mice during chronic exposure to several different doses of 2-acetylaminofluorene (2-AAF) and 4-aminobiphenyl (4-ABP). Continuous oral administration of these compounds for 4 weeks produced an increase in DNA adduct formation during the first 2 weeks...