Exposure to ultrafine particles (UFPs) from vehicle exhaust has been related to risk of cardiovascular and pulmonary disease and cancer, even though exposure assessment is difficult. We studied personal exposure in terms of number concentrations of UFPs in the breathing zone, using portable instruments in six 18-hr periods in 15 healthy nonsmoking subjects. Exposure contrasts of outdoor pollution were achieved by bicycling in traffic for 5 days and in the laboratory for 1 day. Oxidative DNA damage was assessed as strand breaks and oxidized purines in mononuclear cells isolated from venous blood the morning after exposure measurement. Cumulated outdoor and cumulated indoor exposures to UFPs each were independent significant predictors of the level of purine oxidation in DNA but not of strand breaks. Ambient air concentrations of particulate matter with an aero-dynamic diameter of ≤10 μm (PM10), nitrous oxide, nitrogen dioxide, carbon monoxide, and/or number concentration of UFPs at urban background or busy street monitoring stations was not a significant predictor of DNA damage, although personal UFP exposure was correlated with urban background concentrations of CO and NO2, particularly during bicycling in traffic. The results indicate that biologic effects of UFPs occur at modest exposure, such as that occurring in traffic, which supports the relationship of UFPs and the adverse health effects of air pollution.

No abstract

Background: Particulate air pollution is associated with increased risk of cardiovascular events although the involved mechanisms are poorly understood. The objective of the present study was to investigate the effects of controlled exposure to ambient air fine and ultrafine particles on microvascular function and biomarkers related to inflammation, haemostasis and lipid and protein oxidation.

Air pollution, containing high-level of ultrafine particles (UFP) and benzene, is a prominent environmental health problem in many cities of the World. We investigated the level of oxidative DNA damage in mononuclear blood cells (MNBC) by the comet assay as DNA strand breaks (SB) and formamidopyrimidine DNA glycosylase (FPG) sensitive sites in residents from three urban locations in Cotonou, Benin (taxi-moto drivers, subjects living near roads with intense traffic and suburban residents) and rural residents. Exposure was characterized by urinary excretion of S-phenylmercapturic acid (S-PMA), a biomarker of benzene exposure, and by ambient UFP. There were clear stepwise gradients with respect to ambient UFP, S-PMA excretion and oxidative DNA damage with rural subjects < suburban subjects < residents living near highly trafficed roads

Particulate air pollution is associated with increased risk of pulmonary diseases and detrimental outcomes related to the cardiovascular system, including altered vessel functions. This study's objective was too evaluate the effects of ambient particle exposure on the blood-gas permeability, lung function and Clara cell 16 (CC16) protein release in healthy young subjects. Twenty-nine nonsmokers participated in a randomized, two-factor crossover study with or without biking exercise for 180 min and with 24-h exposure to particle-rich (6169-15,362 particles/cm 3 ; 7.0-11.6 µg/m 3 PM 2.5 ; 7.5-15.8 µg/m 3 PM 10−2.5 ) or filtered (91-542 particles/cm 3 ) air collected above a busy street. The clearance rate of aerosolized 99m Tc-labeled diethylenetriamine pentaacetic acid ( 99m Tc-DTPA) was measured as an index for the alveolar epithelial membrane integrity and permeability of the lung blood-gas barrier after rush-hour exposure. Lung function was assessed using body plethysmography, flowvolume curves, and measurements of the diffusion capacity of carbon monoxide. CC16 was measured in plasma and urine as another marker of alveolar integrity. Particulate matter exposure had no significant effect on the epithelial membrane integrity using the methods available in this study. Exercise increased the clearance rate of 99m Tc-DTPA indicated by a 6.8% (95% CI: 0.4-12.8%) shorter half-life and this was more pronounced in men than women. Neither particulate matter exposure nor exercise had an effect on the concentration of CC16 in plasma and urine or on the static and dynamic volumes or ventilation distribution of the lungs. The study thus demonstrates increased permeability of the alveolar blood-gas barrier following moderate exercise, whereas exposure to ambient levels of urban air particles has no detectable effects on the alveolar blood-gas barrier or lung function.

No abstract

Oxidative DNA damage detected by the comet assay as formamidopyrimidine DNA glycosylase (FPG) sensitive sites, almost as a rule is reported as comet assay score rather than numerical sites in the genome, probably because the latter requires X-ray calibration. We compared the ability of five experienced and five inexperienced comet assay investigators to detect a dose-response relationship in irradiated A549 lung epithelial cell culture samples (0, 10 Gy and three samples of 5 Gy), based on an arbitrary five class scoring system. The samples were scored on three different occasions, thus allowing determination of the variation in sample scoring. All investigators qualitatively distinguished between samples in a dose-dependent manner, albeit with large variation in the slope and intercept of dose-response curves. There was a tendency that investigators with experience in scoring A549 cells had more consistent results than experienced investigators who had only scored lymphocytes or inexperienced investigators. The inexperienced investigators improved their scoring ability during the three sessions. Subsequently we showed that the variation in baseline level of FPG modifications in mononuclear blood cells of five healthy humans was lower when investigators used their individual X-ray calibration curve as compared to a common calibration curve. In conclusion, this study showed that comet assay investigators score differently when using a five class scoring system, which indicates that more consistent estimations of FPG sites in the genome are obtained by use of investigators' individual X-ray calibrations.

With use of ibotenic acid as a lead, analogues of (RS)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and of (RS)-3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-7-carboxylic acid (7-HPCA) were synthesized and tested as excitants of neurons in the cat spinal cord by using microelectrophoretic techniques and as inhibitors of the binding of kainic acid in vitro. Like AMPA and 7-HPCA, (RS)-3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5,4-c]-pyridine-5-carboxylic acid (10, 5-HPCA) and (RS)-3-hydroxy-5-(bromomethyl)isoxazole-4-propionic acid (11, ABPA) proved to interact potently and selectively with central quisqualic acid receptors, assumed to represent physiological glutamic acid receptors. Analogues of 7-HPCA or 10, in which one or both of the acid groups were masked, were very weak or inactive as neuronal excitants and had no antagonistic effects at excitatory amino acid receptors. The structure of 7-HPCA in the crystalline state was established by X-ray analyses. The preferred conformation of 10 in aqueous solution was determined by 1H NMR spectroscopy. On the basis of these studies, 7-HPCA as well as 10 were shown to adopt preferentially conformations with the carboxylate groups in equatorial positions. It is suggested that AMPA, 7-HPCA, and 10 interact with quisqualic acid receptors in conformations essentially reflecting active conformation(s) of glutamic acid at these receptors.