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Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis 1999-Mar

Intraindividual variations of DNA adduct levels in humans.

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Absztrakt

Reports on intraindividual changes of DNA adduct levels in humans are rare. Most of the data available in the literature are from polycyclic aromatic hydrocarbons (PAHs) and are measured in white blood cells with 32P-postlabeling or immunochemical assays. Surprisingly, environmental exposure can have a larger effect on PAH adduct levels than occupational exposure, food or smoking. Highest (13-fold) summer/winter increments, due to indoor heating were observed in Gliwice, Poland. Further studies of environmental PAH exposure confirm the environmental influence on intraindividual changes in PAHs-DNA adduct levels: studies of the Teplice program, (Czech Republic) and studies with US soldiers, stationed in Germany who went for a 8-week period of duty to Kuwait. Variations in occupational exposure, e.g., changing of anode material in aluminium plants (elevation factor 3.94), layoffs, reduced working hours in iron foundries or vacation also led to intraindividual changes in PAH adduct levels. Increase in PAH adduct levels after consumption of charcoal broiled meat evidently depends on individual susceptibility, e.g., polymorphism. In one person a 7.4-fold increment was observed. PAH adduct levels were not significantly influenced by smoking cessation whereas sister chromatid exchanges significantly decreased. Changes in occupational exposure to styrene in lamination plants, e.g., due to vacation, did not significantly influence styrene-O6-dG adduct levels in lymphocytes and granulocytes as determined by 32P-postlabeling. Increase of N7-methylguanine and O6-methylguanine levels were followed in white blood cells during treatment of cancer patients with dacarbazine and allowed insights into pharmacokinetic properties. According to a rough estimation the high increment in the PAHs-DNA adduct level of about 13 observed in Gliwice (see above) would result in a tentative increase in cancer risk from about 1 death/107 inhabitants to approximately 10 deaths/107 inhabitants which, in general, is considered as acceptable.

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