POTENTIATION OF OXIDANT-INDUCED TOXICITY IN HAMSTER LUNG SLICES BY DIMETHYLTHIOUREA

Dimethylthiourea (DMTU) is an effective scavenger of reactive oxygen m etabolites. This property has been successfully exploited, experimenta lly, in the protection of cells and tissues against oxidative damage. In this study, however, we have observed that levels of nonprotein sul fhydryls (NPSH) in hamster lung slices were markedly decreased by incu bation with 10 or 40 mM DMTU. These changes were associated with morph ological signs of injury, increased levels of oxidised glutathione (GS SG), and an increased activity of the pentose phosphate pathway (PPP), suggesting that the loss of NPSH was due to their oxidation. Incubati on with 40 mM, but not 10 mM DMTU, also resulted in a decreased abilit y to oxidise 6-C-14glucose or to synthesise proteins, suggesting tha t at the high concentration, DMTU may cause functional impairment of t he tissue. Furthermore, the ability of the slices to accumulate putres cine decreased after incubation with the oxidative toxins paraquat (PQ ), tert-butyl hydroperoxide (t-BOOH) or hydrogen peroxide (H2O2) and w as further decreased by co-incubation with DMTU. Putrescine uptake, a function specific to the alveolar type I and II epithelial cells, was not affected by incubation with DMTU alone. DMTU did not exacerbate th e effect of the nonoxidative toxin iodoacetamide (IAA) on putrescine u ptake but it did affect markers of general cell damage or dysfunction. We suggest, therefore, that the toxicity of oxidants toward lung tiss ue is potentiated in alveolar epithelial cells by DMTU.