Segmentary effects on the renal proximal tubule due to hexachloro-1,3-butadiene in rats: biomarkers related to gender.

Renal tissue biomarkers (glutamine synthetase and p-aminohippuric acid uptake) were studied in male and female rats after treatment with hexachloro-1,3-butadiene. Reduced glutathione content also was also determined in liver and kidney. Histopathological examination (light microscopy) was then performed. The aim was to define sex differences in nephrotoxic effects caused by the solvent injected i.p. at 50, 100 and 200 mg kg(-1) dose. The rats were sacrificed 24 and 48 h after treatment; after 24 h a significant (P < 0.05) dose-dependent depletion of liver reduced glutathione was observed in male rats only; after 48 h male and female rats showed a significant (P < 0.05) increase at 50 and 100 mg kg(-1) doses. Reduced glutathione in the kidney was increased in male but not in female rats 24 and 48 h after treatment. Glutamine synthetase activity in renal tissue showed a significant (P < 0.05) dose-dependent decrease 24 and 48 h after treatment in both sexes, but is was significantly (P < 0.05) greater in female rats after 48 h. p-Aminohippuric acid uptake in renal cortical slices appeared significantly (P < 0.05) decreased in both sexes at the higher dose 24 h after treatment but this was significantly (P < 0.05) greater in female rats. A further significant (P < 0.05) impairment was observed after 48 h in males treated with a 200 mg kg(-1) dose. In addition, a slight but significant (P < 0.05) loss of p-aminohippuric acid uptake was observed 48 h after treatment with a 100 mg kg(-1) dose in both sexes. Light microscopy showed that the pars recta of the proximal tubule was mainly affected and tubular damage increased according to dose and time, involving the inner medulla and cortex. In conclusion, female rats show a significantly earlier and higher susceptibility of the kidney to toxic effects of hexachloro-1,3-butadiene.

Analysis of aromatic DNA adducts in laryngeal biopsies.

Epidemiological studies have confirmed the correlation between tobacco smoking, environmental pollution and the incidence of cancers of the respiratory tract. The occurrence of laryngeal cancer in Poland is relatively high compared to other European countries. Since 1969 the mortality related to larynx cancer appears to be increasing. Tobacco smoke contains an abundance of such carcinogenic compounds as polycyclic aromatic hydrocarbons (PAH), aromatic amines and N-nitrosoamines, which can react with DNA and form adducts. We analyzed aromatic DNA adducts in laryngeal tissues from patients with primary laryngeal, which was confirmed histopathologically to be squamous cell carcinoma. The group consisted of 33 patients (5 women and 28 men). Total laryngectomy was performed in patients. A detergentphenol method was used for DNA isolation. Aromatic DNA adducts were analyzed by a 32P-postlabelling technique with butanol extraction and high performance liquid chromatography. The presence of aromatic DNA adducts was demonstrated in all tissues. Large interindividual differences of DNA adduct levels were seen in each tissue studied. There was a higher mean level of DNA adducts in interarytenoid area non-tumors (51.96/10(8) +/- 91.71 NN) than in non-tumor tissue elsewhere (46.91/10(8) +/- 46.36 NN) and tumor tissue (43.52/10(8) +/- 45.88 NN). Adduct levels were correlated with age, sex, cigarette smoking and TNM stage.

An assessment of indoor air contaminants in buildings with recreational activity.

Indoor air quality measurements were carried out during three concerts and one ice hockey game in three different halls. Gas phase components consisted of CO2, CO, and NO whereas for particulate indicators, measurements of particle mass distributions (0.05-9 microm), particle number distributions (0.75-10 microm), and particle bound polycyclic aromatic hydrocarbons (pPAH) were carried out. The calculated ventilation rates did not meet the ventilation requirements for rooms with occupants who smoke to be perceived as acceptable by 80% of the occupants. Average PM9 (mass of particulate matter with an aerodynamic diameter < 9 microm) concentrations throughout the events ranged from 318 to 2000 microg m(-3). Particle concentrations in the size range < 0.4 microm measured 203-696 microg m(-3), the majority of it being attributed to environmental tobacco smoke (ETS). For particle numbers > 0.75 microm concentrations ranged from 2 x 10(4) to 1.9 x 10(5) particles per l while for pPAH, concentrations from 336 to 990 ng m(-3) were observed. The average event concentrations for the gaseous component CO2 ranged from 1110 to 1700 ppm, for CO 2-3.1 ppm and for NOx 237 ppb. The event to baseline concentration ratios for gaseous components ranged from 1.1 to 4.3 while for particulate indicators generally much greater ratios between 0.7 and 140 were found. Possible health effects inflicted by an exposure based on the measured concentrations of the various parameters are discussed.

Effects of operating variables on PAH emissions and mutagenicity of emissions from woodstoves.

As part of the Integrated Air Cancer Project, the U.S. Environmental Protection Agency (EPA) has conducted field emission measurement programs in Raleigh, North Carolina, and Boise, Idaho, to identify the potential mutagenic impact of residential wood burning and motor vehicles on ambient and indoor air. These studies included the collection of emission samples from chimneys serving wood burning appliances. Parallel projects were undertaken in instrumented woodstove test laboratories to quantify woodstove emissions during operations typical of in-house usage but under more controlled conditions. Three woodstoves were operated in test laboratories over a range of burnrates, burning eastern oak, southern yellow pine, or western white pine. Two conventional stoves were tested at an altitude of 90 m. One of the conventional stoves and a catalytic stove were tested at an altitude of 825 m. Decreasing burnrate increased total particulate emissions from the conventional stoves while the catalytic stove's total particulate emissions were unaffected. There was no correlation of total particulate emissions with altitude whereas total polynuclear aromatic hydrocarbon (PAH) emissions were higher at the lower altitude. Mutagenicity of the catalytic stove emissions was higher than emissions from the conventional stove. Emissions from burning pine were more mutagenic than emissions from oak.

Lipid peroxidation: a possible mechanism of trichloroethylene-induced nephrotoxicity.

The purpose of this study was to investigate whether lipid peroxidation plays a role in (TCE) trichloroethylene-induced nephrotoxicity in mice at different oxygen concentrations. Male NMRI mice (25-30 g) were treated i.p. with TCE in a dosage of 125-1000 mg/kg in sesame oil. To determine the TCE-induced depletion of reduced glutathione (GSH) in the kidney cortex and liver tissue, mice were given 1000 mg/kg TCE i.p., then killed between 0 and 6 h after TCE administration and GSH was measured was non-protein sulfhydryls. In another series of experiments, mice were administered 125 to 1000 mg/kg TCE i.p. with or without a 2 h i.p. pretreatment with 1500 mg/kg L-buthionine-S-R-sulfoximine (BSO). Mice were then exposed to a 10, 15, 20 or 100% oxygen atmosphere for 3 h and lipid peroxidation in vivo was measured as exhalation of ethane. Subsequently, mice were killed and malondialdehyde (MDA) generation was measured in the liver and kidney cortex. Ethane evolution was estimated by gas chromatography and MDA was determined as thiobarbituric acid reactive substances. In a further series of experiments mice were treated in the same manner as for ethane and MDA determination and the changes in blood urea nitrogen (BUN) and accumulation of the organic ion p-aminohippurate (PAH) were determined. PAH accumulation by renal cortical slices were measured as the slice to medium (S/M) ratio. Six hours after administration of 1000 mg/kg TCE to mice, GSH was significantly depleted to about 60% of control in the kidney cortex but not in the liver. Three hours after TCE administration, MDA content in the kidney cortex and ethane exhalation increased in a dose-dependent manner only under a 10% oxygen atmosphere. Under the same experimental conditions, MDA content remained unchanged in the liver. BSO depletion of GSH prior TCE administration induced an increase of the MDA content in the kidney cortex and an increase of the ethane exhalation in vivo. At 10% oxygen concentration, TCE induced a dose-dependent increase in BUN and a dose-dependent decrease of PAH accumulation by the renal cortical slices. Thus, the results of the present study suggest that, under hypoxic conditions, lipid peroxidation plays a role in TCE nephrotoxicity.

Mutagenicity and PAH content of airborn particulates and of fallen dusts from two Hungarian towns and emission samples from aluminum reduction and power plants.

Urban air particulates (suspended particles and settling dust), furthermore dust emitted by a Soderberg aluminum reduction plant and a coal burning power plant from an industrial town, Ajka (30,000 inhabitants) were analysed for PAH content (liquid chromatography) and mutagenicity (Salmonella microsome test). Air particulates from Papa--a town of similar size without considerable heavy industry--and corresponding plant emission from Inota, a third town in the study, served as controls. The dust content and the PAH concentration, as well as the mutagenic potency of the air in Ajka were higher than in Papa. Mutagenicity of the airborne particulates showed a clear seasonality with a winter maximum and a summer minimum in both towns. The mutagenic potency of air correlated well with the air BaP and total PAH content in Ajka, but not in Papa. The amounts of extractable organic material and mutagenic potency as calculated for unit quantity of airborne particulate matter was higher in the Papa samples. Similar differences between the two towns were observed in the case of fallen dust, too. On the basis of examination of emitted dust, it can be stated, that in the mutagenicity of urban air, the aluminum plant emission plays a considerably higher role than the power plant emission, which is the main component of air dust pollution in Ajka.

PAH excretion in two species of cancroid crab Cancer irroratus and C. borealis.

To determine the characteristics of p-aminohippuric acid (PAH) excretion in Cancer irroratus and C. borealis, crabs were given a single injection of radiolabeled PAH and polyethylene glycol (PEG), and serum, urine, tissue, and seawater concentrations of each were measured over the next 6 days. In both species, PEG clearances averaged 5-10 ml serum/day; serum PAH concentrations fell exponentially after a 1-day equilibration period. In C. irroratus, urine PAH rose over the first 2 days and then fell; during days 2-6, mean urine PAH averaged two to four times mean serum PAH. In C. borealis, urine-to-serum ratios for PAH were 20-40 during days 2-6. PAH-to-PEG clearance ratios exceeded unity in both species, with ratios in C. borealis about three to six times those in C. irroratus. Tissue distribution data showed that C. irroratus midgut gland accumulated up to 50% of injected PAH, with gland-to-serum concentration ratios of 15-45; in this species, stomach fluid-to-serum PAH concentration ratios averaged 87, and nonurinary routes accounted for more than half of excreted PAH. In C. borealis, midgut gland-to-serum ratios never exceeded 2, and the urinary routes accounted for all excreted PAH. Thus, in C. irroratus, injected PAH accumulated in the midgut gland, with slow excretion through renal and nonrenal routes; in C. borealis, PAH remained in hemolymph, and only the renal route of excretion was utilized.

Simultaneous determination of p-aminobenzoic acid, acetyl-p-aminobenzoic acid and p-aminohippuric acid in serum and urine by capillary gas chromatography with use of a nitrogen-phosphorus detector.

In various studies during recent years, the use of p-aminobenzoic acid has been described in screening tests for exocrine pancreatic function. A synthetic three-unit compound N-benzoyl-L-tyrosyl-p-aminobenzoic acid has been administered orally and hydrolysed in the small intestine in the presence of chymotrypsin to N-benzoyl-L-tyrosine and p-aminobenzoic acid. This study describes a convenient procedure in which, after a selective extraction and derivatization with diazomethane, capillary gas chromatography is used combined with nitrogen-sensitive detection. With the proposed procedure, p-aminobenzoic acid and its major metabolites, acetyl-p-aminobenzoic acid and p-aminohippuric acid, can be monitored in serum and in urine samples.