The effect of exposure to carcinogenic polycyclic aromatic hydrocarbons adsorbed onto respirable air particles (PM2.5, diameter < 2.5 μm) on DNA adducts and chromosomal aberrations was repeatedly studied in Prague, Czech Republic, in groups of policemen working in the downtown area and in bus drivers. Personal exposure was evaluated using personal samplers during working shifts. DNA adducts wer...

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 acids increased malonaldehyde-derived...

The tumor suppressor gene p53 is frequently mutated in cigarette smoke (CS)-related lung cancer. The p53 binding pattern of carcinogenic polycyclic aromatic hydrocarbons (PAHs) found in CS coincides with the p53 mutational pattern found in lung cancer, and PAHs have thus been considered to be major culprits for lung cancer. However, compared with other carcinogenic compounds, such as aldehydes,...

A 32P-postlabeling assay was employed for detection and quantitation of DNA adducts formed with carcinogenic 1-phenylazo-2-hydroxynaphthalene (Sudan I, Solvent Yellow 14) activated by a peroxidase system. Enrichment of adducts by digestion with nuclease P1 or by extraction into n-butanol prior to 32P-labeling was used. Both enrichment procedures exhibited comparable results for recovery of indi...

Previous studies by us and others have shown a significantly higher level of aromatic DNA adducts in normal adjacent breast tissue samples obtained from breast cancer patients than in those obtained from non-cancerous controls. The increased amount of DNA damage could be related to excess environmental carcinogen exposure and/or genetic susceptibility to such exposure. In the current study, we ...

The dose dependency of the binding of benzo(a)pyrene (BaP) with DNA of mouse epidermis was investigated. BaP-conjugated epidermal DNA was isolated and enzymatically degraded to deoxyribonucleosides. The BaP-DNA adducts were separated by Sephadex LH-20 column or high-performance liquid chromatography. Two major BaP-DNA adducts were found. One was in the region of the elution profile that contain...

The drug tamoxifen shows evidence of genotoxicity, and induces liver tumours in rats. Covalent DNA adducts have been detected in the liver of rats treated with tamoxifen, and these arise through metabolism at the alpha-position to give an ester which reacts with DNA. (E)-1-(4-iodophenyl)-2-phenyl-1-[4-(2-pyrrolidinoethoxy)phenyl]-but-1-en e (idoxifene) is an analogue of tamoxifen in which forma...

Tobacco smoking causes not only lung cancer but also cancer of the oral and nasal cavities, oesophagus, larynx, pharynx, pancreas, liver, kidney, stomach, urinary tract and cervix. Tobacco smoke contains many carcinogens that exert their biological effects through interaction of reactive intermediates with DNA to form DNA adducts. The same electrophilic species also react with cellular proteins...

DNA adducts are frequently caused by chemical induced changes in DNA. If mis-repaired, they can lead to nucleotide substitutions, deletions or chromosomal rearrangements. Depending on adduct stereochemistry and properties of the DNA target, adducts can inhibit transcriptional mechanisms. Here we demonstrate how this phenomenon can be exploited to detect DNA adducts in individual nematodes (Caen...

An improved high-performance liquid chromatography/fluorometric assay has been established to quantitate the benzo(«)pyrene (BP) tetrols released after acid hydrolysis of lung DN A from lung cancer patients, so that the formation of benzo(a)pyrene diol-epoxide-DNA adducts can be measured. The r-7,c-10,f-8,f-9-tetrahydroxy-7,8,9,10-tetrahydro-BP isolated by high-performance liquid chromatograph...