• Effects of an acute exposure to toluene on the DNA repair activity of the human 8-oxoguanine DNA glycosylase 1 (hOGG1) in healthy subjects.

      Finkenwirth, P.; Spelmeyer, U.; Hommel, G.; Rose, D.-M.; Jung, D.; Rossbach, B.; Mayer-Popken, O.; Platt, K.-L.; Oesch, F.; Muttray, A. (2009-08)
      The structure and previous studies on the biotransformation of toluene lead to the suspicion that metabolites may be formed which preferentially react with strongly nucleophilic partners such as sulfhydryl groups of cysteines in proteins. Human 8-oxoguanine DNA glycosylase 1 removes the major oxidative DNA damage and possesses eight cysteines. Its potential inactivation may lead to accumulation of DNA damage by reactive oxygen species formed by exogenous agents or by ubiquitous endogenous processes. The goal of the present investigation was to study the in vivo effect in humans of an acute toluene exposure on hOGG1 activity. Twenty healthy, non-smoking males were exposed to 50 ppm toluene and to filtered air in an exposure chamber for 270 min, using a cross-over design. Before and 30 min after the end of exposure, blood samples were taken and toluene concentrations and the hOGG1 activity were measured. hOGG1 activity was determined in peripheral mononuclear blood cells. Thirty minutes after exposure to toluene, we found a median blood concentration of 0.25 mg toluene/l. Compared with the activity before exposure, upon exposure to toluene a statistically insignificant median increase of hOGG1 activity by +0.4% and upon exposure to air by +2.3% was determined. Thus, no reduction of the hOGG1 repair activity after acute exposure to 50 ppm toluene was observed.
    • New aspects on mechanisms of chemical carcinogenesis: emphasis on species and gender/sex differences and developmental/aging determinants.

      Oesch, Franz; Dietrich, Cornelia; Naegeli, Hanspeter; Schwarz, Michael; van der Horst, Gijsbertus; Zanger, Ulrich; Oesch, Barbara; Weiss, Carsten (2008-11)