Faculty Bibliography

Ozone (O3) and nitrogen dioxide (NO2) are common air pollutants, and exposure to these gases has been shown to affect pulmonary physiology, biochemistry, and structure. This study examined their ability to modulate arachidonic acid metabolites (eicosanoids) in the lungs. Rabbits were exposed for 2 h to O3 at 0.1, 0.3, or 1 ppm; NO2 at 1, 3, or 10 ppm; or to a mixture of 0.3 ppm O3 and 3 ppm NO2. Groups of animals sacrificed either immediately or 24 h after each exposure underwent broncho-pulmonary lavage. Selected eicosanoids were assessed in lavage fluid by radioimmunoassay. Increases in prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha) were found immediately after exposure to 1 ppm O3. Exposure to 10 ppm NO2 resulted in a depression of 6-keto-PGF1 alpha, while thromboxane B2 (TxB2) was elevated after exposure to 1 ppm NO2 and depressed following 3 and 10 ppm. The O3/NO2 mixture resulted in synergistic increases in PGE2 and PGF2 alpha, with the response appearing to be driven by O3. This study has demonstrated that acute exposure to either O3 or NO2 can alter pulmonary arachidonic acid metabolism and that the responses to these oxidants differ, both quantitatively and qualitatively

Inhaled acidic sulfate aerosols affect various aspects of lung function, presumably by delivery of hydrogen ion (H+) to target sites. Recent evidence suggests that the relationship between response and H+ content of the exposure atmosphere may depend upon the specific sulfate species with which the H+ is associated. This study examined comparatively the effects of exposure to the two main ambient acidic sulfates, sulfuric acid (H2SO4) and ammonium bisulfate (NH4HSO4), using the phagocytic activity of alveolar macrophages as the endpoint. Rabbits were exposed to 250-2000 micrograms/m3 H2SO4 (as SO4(-2)) and 500-4000 micrograms/m3 NH4HSO4 (as SO4(-2)) for 1 hr/day for 5 days; bronchopulmonary lavage was then performed for recovery of free lung cells. Phagocytosis, measured by uptake of opsonized latex spheres in vitro, was altered by exposure to H2SO4 at concentrations greater than or equal to 500 micrograms/m3 and to NH4HSO4 at greater than or equal to 2000 micrograms/m3. Assessment of results in terms of the calculated hydrogen ion concentration in the exposure atmosphere showed that identical levels of H+ produced different degrees of response depending upon whether exposure was to H2SO4 or NH4HSO4. On the other hand, macrophages incubated in acidic environments in vitro responded similarly regardless of whether H2SO4 or NH4HSO4 was used to adjust the pH. Possible reasons for the difference in response observed in vivo and in vitro are discussed. Speciation of ambient acidic sulfate aerosols may be needed in atmospheric monitoring so as to assess the presence of H+ posing the greatest biologic hazard following inhalation exposure

Eicosanoids (arachidonic acid metabolites) are potent biological mediators. Modulation of their metabolism by air pollutants may be a possible factor in the pathogenesis of environmentally related lung disease. Sulfuric acid (H2SO4) aerosols are components of ambient air in many areas. Rabbits were exposed to H2SO4 (0.3 microns) at 250, 500, or 1000 micrograms/m3 for 1 hr/day for 5 days. They were then euthanized, the lungs lavaged, and eicosanoid analyses performed by radioimmunoassay of acellular lavage fluid. An exposure-concentration-dependent decrease in levels of prostaglandins E2 and F2 alpha and thromboxane B2 was found; no change in leukotriene B4 was observed. Tracheal explants exposed to acidic environments in vitro also showed reduced production of PGE2, PGF2 alpha, and TxB2. Incubation with sodium sulfate (Na2SO4) showed no effect of the sulfate ion (SO4(2-)). This study, the first to examine eicosanoid production after in vivo exposure to pure H2SO4 droplets, indicates that such exposure can modulate arachidonic acid metabolism, and that this is likely due to the deposition of hydrogen ion (H+) on target tissue

We have investigated the activity of insoluble and soluble lead compounds in inducing mutagenesis, cell transformation and sister chromatid exchange in mammalian cells. Insoluble lead sulfide, readily phagocytized, was more than four times as toxic to V79 cells on a microM basis, than two moderately soluble lead compounds although the exposure time for the soluble salts was five times longer. These findings demonstrate the importance of different cellular mechanism(s) of metal uptake and bioavailability. Both insoluble lead sulfide and more soluble lead nitrate were mutagenic at the HPRT locus in V79 cells. Although less mutagenic at the higher concentrations, lead nitrate at a concentration of 500 microM enhanced the mutation frequency greater than 6-fold above background following a 5-day exposure. Although the mechanism(s) by which lead induces mutations is unknown, failure of both compounds to induce SCE and DNA single-strand breaks, detectable by alkaline elution, suggests that lead-induced mutations may not be a result of direct damage to DNA but may occur via indirect mechanisms including disturbances in enzyme functions important in DNA synthesis and/or repair, or in DNA-helical structure. Lead acetate also transformed SHE cells in a dose-response fashion following a 48-h exposure. Our results indicate that lead compounds may be genotoxic by an indirect mechanism, and lend support to the view that lead is a carcinogen

The pharmacokinetics of sulfadimethoxine (SDM) blood clearance, gastrointestinal absorption and tissue distribution and elimination were determined in channel catfish (Ictalurus punctatus) after intravenous and oral dosing using radiolabelled SDM. Blood clearance of SDM in catfish was rapid compared to mammals when the drug was given iv. Results from in vitro equilibrium dialysis studies suggest that this is due to a lower binding of SDM to plasma proteins in fish (18.4%) compared to mammalian species (60-88%). Results from oral dose studies indicated that SDM is readily absorbed from the gastrointestinal tract in channel catfish and distributes rapidly to body tissues, primarily the muscle. With time, concentrations of SDM in muscle decrease and the drug accumulates in the bile, primarily as the N-acetyl-metabolite