Effects of paving asphalt fume exposure on genotoxic and mutagenic activities in the rat lung

Asphalt fumes are complex mixtures of aerosols and vapors containing various organic compounds, including polycyclic aromatic hydrocarbons (PAHs). Previously, we have demonstrated that inhalation exposure of rats to asphalt fumes resulted in dose-dependent induction of CYP1A1 with concomitant down-regulation of CYP2B1 and increased phase II enzyme quinone reductase activity in the rat lung. In the present study, the potential genotoxic effects of asphalt fume exposure due to altered lung microsomal enzymes were studied. Rats were exposed to air or asphalt fume generated under road paving conditions at various concentrations and sacrificed the next day. Alveolar macrophages (AM) were obtained by bronchoalveolar lavage and examined for DNA damage using the comet assay. To evaluate the systemic genotoxic effect of asphalt fume, micronuclei formation in bone marrow polychromatic erythrocytes (PCEs) was monitored. Lung S9 from various exposure groups was isolated from tissue homogenates and characterized for metabolic activity in activating 2-aminoanthracene (2-AA) and benzo[a]pyrene (BaP) mutagenicity using the Ames test with Salmonella typhimurium YG1024 and YG1029. This study showed that the paving asphalt fumes significantly induced DNA damage in AM, as revealed by DNA migration in the comet assay, in a dose-dependent manner, whereas the micronuclei formation in bone marrow PCEs was not detected even at a very high exposure level (1733 mg h/m3). The conversion of 2-AA to mutagens in the Ames test required lung S9-mediated metabolic activation in a dose-dependent manner. In comparison to the controls, lung S9 from rats exposed to asphalt fume at a total exposure level of 479+/-33 mg h/m3 did not significantly enhance 2-AA mutagenicity with either S. typhimurium YG1024 or YG1029. At a higher total asphalt fume exposure level (1150+/-63 mg h/m3), S9 significantly increased the mutagenicity of 2-AA as compared to the control. However, S9 from asphalt fume-exposed rats did not significantly activate the mutagenicity of BaP in the Ames test. These results show that asphalt fume exposure, which significantly altered both phases I and II metabolic enzymes in lung microsomes, is genotoxic to AM and enhances the metabolic activation of certain mutagens through altered S9 content.     

Short-term exposure to zinc- and copper-containing welding fumes: Effects on pulmonary function in humans

Zinc- and copper-containing welding fumes typically induce a systemic inflammation indicated by increase in C-reactive protein (CRP) levels, also known as welding fume fever. It typically includes symptoms like fever, myalgia or headaches, but only a quarter of patients experience respiratory symptoms, e.g. coughing. This retrospective analysis of data of three studies with either control (filtered air) or zinc- and copper-containing welding fume exposure aims to identify and characterize the effect of the welding fumes on lung function. Spirometry and body plethysmography data of male healthy volunteers were analyzed and comparisons between different timepoints after a 6 h exposure were conducted. For controls no significant changes in spirometry were observed between baseline and 6 h, 24 h and 1 week after exposure. For volunteers exposed to zinc- and copper-containing welding fumes no significant reductions in forced expiratory volume in 1 s (FEV1) and minimal reductions in vital capacity (VC) (52 ml, 0.9%) were detected after 6 h. After 24 h significant reductions in FEV1 (147 ml, 3.2%) and VC (162 ml, 2.9%) could be observed. 1 week after exposure FEV1 was still significantly reduced (102 ml, 2.1%) and airway resistance were increased while no differences in VC were detected. The reduction of FEV1% after 24 week significantly correlated with increases in CRP levels. In conclusion, a single exposure to zinc- and copper-containing welding fumes leads not only to a systemic inflammation but could also induce slight sustained airway constrictions after 24 h and 1 week. The observed slight airway constriction is not caused by immediate effects but possibly inflammatory processes. Although welding fume fever does not necessarily present respiratory symptoms, welders exposed to zinc- and copper-containing welding fumes should be monitored for respiratory symptoms and obstructive ventilation pattern.     

Genotoxic risk assessment of pathology and anatomy laboratory workers exposed to formaldehyde by use of personal air sampling and analysis of DNA damage in peripheral lymphocytes

A study was conducted to evaluate the genotoxic effect of occupational exposure to formaldehyde on pathology and anatomy laboratory workers. The level of exposure to formaldehyde was determined by use of passive air-monitoring badges clipped near the breathing zone of 59 workers for a total sampling time of 15min or 8h. To estimate DNA damage, a chemiluminescence microplate assay was performed on 57 workers before and after a 1-day exposure. Assessment of chromosomal damage was carried out by use of the cytokinesis-blocked micronucleus assay (CBMN) in peripheral lymphocytes of 59 exposed subjects in comparison with 37 controls matched for gender, age, and smoking habits. The CBMN assay was combined with fluorescent in situ hybridization with a pan-centromeric DNA probe in 18 exposed subjects and 18 control subjects randomized from the initial populations. Mean concentrations of formaldehyde were 2.0 (range <0.1-20.4ppm) and 0.1ppm (range <0.1-0.7ppm) for the sampling times of 15min and 8h, respectively. No increase in DNA damage was detected in lymphocytes after a one-workday exposure. However, the frequency of binucleated micronucleated cells was significantly higher in pathologists/anatomists than in controls (16.9 per thousand+/-9.3 versus 11.1 per thousand+/-6.0, P=0.001). The frequency of centromeric micronuclei was higher in exposed subjects than in controls (17.3 per thousand+/-11.5 versus 10.3 per thousand+/-7.1) but the difference was not significant. The frequency of monocentromeric micronuclei was significantly higher in exposed subjects than in controls (11.0 per thousand+/-6.2 versus 3.1 per thousand+/-2.4, P<0.001), while that of the acentromeric micronuclei was similar in exposed subjects and controls (3.7 per thousand+/-4.2 and 4.1 per thousand+/-2.7, respectively). The enhanced chromosomal damage (particularly chromosome loss) in peripheral lymphocytes of pathologists/anatomists emphasizes the need to develop safety programs.     

大剂量电离辐射对小鼠肺组织的影响

目的探讨大剂量电离辐射对小鼠肺的影响。方法 60Coγ照射小鼠,HE染色观察小鼠肺组织损伤,免疫组化检测小鼠肺转化生长因子β1(TGFβ1)和细胞间粘附因子1(ICAM1)的表达。结果大剂量照射后3d,小鼠肺发生明显异常病变,TGFβ1和ICAM1表达量明显增加。结论肺内皮细胞损伤和血管内物质外漏可能是急性放射性肺损伤的早期重要事件,早期检测ICAM1有助于预测急性放射性肺损伤的发生程度。     

Respiratory response to formaldehyde and off-gas of urea formaldehyde foam insulation.

In 18 subjects, 9 of whom had previously complained of various nonrespiratory adverse effects from the urea formaldehyde foam insulation (UFFI) in their homes, pulmonary function was assessed before and after exposure in a laboratory. On separate occasions formaldehyde, 1 part per million (ppm), and UFFI off-gas yielding a formaldehyde concentration of 1.2 ppm, were delivered to each subject in an environmental chamber for 90 minutes and a fume hood for 30 minutes respectively. None of the measures of pulmonary function used (forced vital capacity, forced expiratory volume in 1 second or maximal midexpiratory flow rate) showed any clinically or statistically significant response to the exposure either immediately after or 8 hours after its beginning. There were no statistically significant differences between the responses of the group that had previously complained of adverse effects and of the group that had not. There was no evidence that either formaldehyde or UFFI off-gas operates as a lower airway allergen or important bronchospastic irritant in this heterogeneous population.     

Cytogenetic analysis of nasal mucosa cells and lymphocytes from high-level long-term formaldehyde exposed workers and low-level short-term exposed waiters

The evidence for genotoxic potential of formaldehyde (FA) in humans is insufficient and conflicting. We previously reported a higher frequency of micronuclei in nasal and oral exfoliative cells from students exposed to formaldehyde vapor for short-term. To further evaluate the genetic effects of long-term occupational exposure to FA and short-term exposure to FA of indoor sources, the frequencies of micronuclei (MN) in nasal mucosa cells, sister chromatid exchanges (SCEs) of peripheral lymphocytes, and the lymphocyte subsets were evaluated in 18 non-smoking workers (mean exposure duration was 8.6 years) in an FA factory and 16 non-smoking waiters exposed to FA for 12 weeks in a ballroom. A non-smoking student group without occupational exposure (n=23) to FA was used as control. The 8h time-weighted average (TWA) concentrations of formaldehyde was 0.985+/-0.286 mg/m3 with the ceiling exposure concentration of 1.694 mg/m3 in the workshop, and 0.107+/-0.067 mg/m3 in the ballroom (5 h TWA). Higher frequencies of micronuclei per thousand cells in nasal mucosa cells of workers versus control (2.70+/-1.50 versus 1.25+/-0.65, p<0.05) and higher frequency of SCEs in peripheral lymphocytes of workers group (8.24+/-0.89 versus 6.38+/-0.41, p<0.05) were observed. Increased frequency of micronuclei in nasal mucosa cells or SCE in peripheral lymphocytes was not found among waiters group. The results suggest that the genotoxic potential of high level FA exposure may have occupational risks in long-term exposure groups.     

核辐射对大深度快速上浮脱险致减压病大鼠相关指标的影响*

目的: 探讨不同剂量核暴露后不同时间对大深度快速上浮脱险致减压病大鼠模型的发病率、死亡率及损伤指标的影响。方法: 80只SD雄性大鼠,随机分成空白对照组、脱险对照组和6个干预组(4 Gy辐射后4 h脱险、6 Gy辐射后4 h脱险、12 Gy辐射后4 h脱险、4 Gy辐射后8 h脱险、6 Gy辐射后8 h脱险、12 Gy辐射8 h后脱险),每组10只。干预组动物先采用不同剂量γ射线外照射(4、6、12 Gy),再进行大深度快速上浮脱险实验(最大加压深度150 m),分析大鼠肺W/D、脾指数及血浆IL-1β的变化。结果: 与脱险对照组比较,核辐射后脱险大鼠的减压病发病率及死亡率明显上升。4 Gy、6 Gy照射4 h后上浮脱险的大鼠发病率和死亡率较照射8 h后高。12 Gy辐射后4 h及8 h脱险大鼠的减压病的发病率及死亡率均比低剂量照射组明显增高,死亡率尤其明显。和发病率及死亡率的变化相一致,肺组织湿/干比、肺组织病理损伤程度、脾指数下降也表现同样的变化趋势:较低剂量(4 Gy、6 Gy)辐射后4 h改变明显,8 h改变不明显,而高剂量(12 Gy)辐射后4、8 h均变化明显。和空白对照组及脱险对照组相比较,各辐射后脱险组的血浆IL-1β浓度均显著上升。结论: 核辐射引起放射性肺损伤、免疫功能下降及血浆炎症因子浓度升高,会增加大鼠快速上浮脱险致减压病的风险。     

Genotoxic effects of bitumen fumes in Big Blue transgenic rat lung

Road paving workers are exposed to bitumen fumes (CAS No. 8052-42-4), a complex mixture of volatile compounds and particles containing carcinogenic and non-carcinogenic polycyclic aromatic hydrocarbons. However, epidemiological and experimental animal studies failed to draw unambiguous conclusions concerning their toxicity. In order to gain better insights on their genotoxic potential, we used an experimental design able to generate bitumen fumes at road paving temperature (temperature: 170 degrees C, total particulate matter: 100mg/m3) and perform a nose-only exposure of Big Blue transgenic rodents 6h/day for five consecutive days. The mutagenic properties of bitumen fumes were determined by analyzing the mutation frequency and spectrum of the neutral reporter gene cII inserted into the rodent genome. We previously observed in mouse lung, that bitumen fumes did not induce an increase of cII mutants, a modification of the mutation spectrum, nor the formation of DNA adducts. Since DNA adducts were found in the lungs of rats exposed to asphalt fumes in similar conditions, we decided to carry out an analogous experiment with Big Blue rats. A DNA adduct was detected 3 and 30 days after the end of treatment suggesting that these genetic alterations were quite steady. Thirty days after exposure, the cII mutant frequency was similar in control and exposed rats. In addition, a slight but not significant modification of the mutation spectrum associated with an increase of G:C to T:A and A:T to C:G transversions was noticeable in the treated animals. Then, these data failed to demonstrate a pulmonary mutagenic potential for bitumen fumes generated at road paving temperature in our experimental conditions despite the presence of a DNA adduct. These results may provide information concerning the pulmonary mechanism of action of this aerosol and may contribute to the occupational health hazard assessment.     

Effects of welding fumes on haematological parameters of male albino rats (Rattus norvegicus)

Welders or metal workers not being an exception are exposed to metals ions or oxides (fumes) at trace concentrations either through direct contact supplementation at occupational sites or indirectly through uptake from contaminated food, water or contaminated soil, dust, or air. The study aims to determine the effects of welding fumes exposure on haematological parameters in blood of experimental animals. The fumes were collected from welding sites during the activity by a skilled welder. 130 male experimental animals were utilized and made into 13 groups. 12 groups were given dosages calculated to correspond to real life workers exposure regimes and 1 group served as control. The dosages were administered intratracheally after been anaesthetized weekly for 12 weeks. The animals were sacrificed and whole blood samples were taken which was then subjected to haematological analysis. The parameters have revealed changes in values whereby RBC, WBC, % lymphocytes, HGB, HCT, MCV, MCH, PLT, PCT and P-LCC have exceeds the control groups values. There was an increase across the treatment groups. However, lymphocytes, MID, granulocytes, % granulocytes, MCHC and MPV have values which were less than the control and no different from one another statistically. This indicates that exposure to welding fumes could cause alterations to most RBC, WBC and PLT indices majorly by effecting an increase. Further studies should be carried out on the response of other markers of toxicity so as to have a broad perception of the effects.     

维生素E对暴露于高温及PM2.5中COPD大鼠呼吸系统的保护性作用*

目的:探讨维生素E改善暴露于高温与PM_2.5对慢性阻塞性肺疾病(COPD)大鼠呼吸系统功能损伤的作用。方法:将54只7周龄SPF级雄性Wistar大鼠随机分成9个实验组(n=6),利用烟草烟雾和气管内滴注脂多糖建立COPD大鼠模型,而后对其进行PM_2.5(0 mg/ml、3.2 mg/ml)气管滴注染毒和维生素E腹腔注射(20 mg/ml)干预,随后高温组进行高温(40℃)暴露,每天一次(8 h),持续3 d。末次暴露后检测肺功能,HE染色制作肺组织病理切片,采用试剂盒测定大鼠肺组织中诱导性一氧化氮合酶(iNOS)、肿瘤坏死因子(TNF-α)、单核细胞趋化蛋白1(MCP-1)的表达水平。结果:与对照组相比,高温和PM_2.5暴露使COPD大鼠肺功能降低(P＜0.05),各PM_2.5染毒组中MCP-1含量均有显著升高(P＜0.05),高温组中iNOS活性显著增高(P＜0.05);与单纯PM_2.5染毒组相比,在常温健康和高温COPD维生素E干预组的TNF-α含量均显著降低(P＜0.05),三组维生素干预组中MCP-1含量均显著降低(P＜0.05),高温COPD维生素干预组中iNOS活性显著降低(P＜0.05)。结论:高温与PM_2.5可引起并进一步加重COPD大鼠的炎症反应,维生素E作为一种抗氧化剂,可明显改善上述损伤作用,从而保护机体。     

Occupational exposure and respiratory health of workers at small scale industries

Certain occupations like welding, painting, and vehicle repairing are associated with regular exposure to dust, exhausts, fuels, fumes, PM, and vapors of welding, solvents, and paint. Many studies have proved a reduction in lung functions due to exposure to these agents. The present study aims to assess and compare respiratory symptoms and pulmonary functions among exposed and non-exposed persons as well as suggests controls respectively. A cross-sectional case study was carried out among small scale industry workers having matched demographic and anthropometric parameters. Medical Research Council (MRC) questionnaire and Micro Direct computerized automated spirometer were used for recording respiratory ailments and pulmonary function tests (PFT) respectively. The percentages of mechanics, welders and painters were 40.9, 31.8, and 27.3 respectively. The highest reported respiratory symptom was chest tightness and whistling among exposed (22.7%) and unexposed (10%). Among study exposed cases, the occupational exposure was found as often (22.7%), sometimes (68.2%) and never (9.1%) while the reported use of airway protection (masks) was very low. Overall respiratory health of the exposed versus controls was reported as excellent (54.5% vs 73.4%), good (27.3% vs 23.3%) and average (18.2% vs 3.3%) respectively. The exposed group on contrary to control one has decreased mean values for FEV1 (3.12 vs 3.50), FVC (4.12 vs 4.43), FEV1/ FVC % (79.60 vs 80.79) and PEF (414.77 vs 523.16). The present study reveals that exposed workers are at increased risk of developing respiratory symptoms and decreased pulmonary functions as compared to unexposed. Such exposure research studies are instrumental in health status evaluation of workers. However, this area has been neglected by the researchers in Saudi Arabia. It is, thus, strongly recommended to carry out prospective studies to substantiate the study results including large sample size, background pollutants concentrations and biological monitoring. Control strategies should be adopted to reduce the vapor concentration in the ambient air, protect and promote respiratory health of workers.     

Effects of Benzo(a)pyrene on Seabass (Dicentrarchus labrax L.): Biomarkers,Growth and Behavior

The main purpose of this study was to investigate the effects of benzo(a)pyrene (BaP) on seabass (Dicentrarchus labrax) juveniles using parameters at different levels of biological organization. Liver antioxidant status, BaP biotransformation and accumulation, growth, and behavior were determined in juveniles after 28 d exposure to BaP (1–16 μ g/l). Liver ethoxyresorufin O-deethylase increased in seabass exposed to 1–8 μ g/l of BaP. Liver glutathione S-transferases and catalase activities were significantly increased at 4 and 8 μ g/l, but a slight decrease was observed at the highest concentrations tested. Bile BaP metabolites were significantly different from the control group at 1 and 16 μ g/l BaP. Liver BaP metabolites and lipid peroxidation significantly increased at 8 and 16 μ g/l BaP. These results suggest that BaP metabolites' accumulation induces oxidative damage in seabass liver. Body weight and length increase were significantly reduced in fish exposed to BaP, with LOECs of 16 and 4 μ g/l, respectively. Food intake and swimming velocity were significantly decreased after exposure to BaP, with LOEC values of 16 and 8 μ g/l, respectively. Results suggest that at concentrations of BaP equal or higher than 8 μ g/l, the detoxification capacity decreases, an accumulation of liver BaP metabolites occurs causing lipid peroxidation, affecting growth and swimming capability of fish.     

急性臭氧暴露对大鼠肺部细胞遗传毒性的影响*

目的: 探讨不同浓度臭氧急性暴露对大鼠肺部细胞的遗传毒性的影响。方法: 36只wistar大鼠随机分为对照组(过滤空气暴露)、臭氧暴露组(0.12 ppm、0.5 ppm、1.0 ppm、2.0 ppm、4.0 ppm)共6组,每组6只。以不同浓度的臭氧对大鼠进行动态染毒4 h后,取肺组织并分离单细胞,采用酶联免疫吸附法检测8-羟基脱氧鸟苷(8-OHdG),利用彗星实验、微核试验和DNA-蛋白质交联实验进行DNA和染色体损伤分析。结果: 与对照组相比,肺组织中8-OHdG含量从臭氧暴露浓度为0.12 ppm起即显著增加,在0.5 ppm时达到最高值。随着臭氧暴露浓度升高,彗星拖尾率逐渐上升,且存在明显的剂量-效应关系;DNA-蛋白质交联率有先升高后下降的趋势,且在2.0 ppm时达到最大值;而肺部细胞微核率尽管呈现出上升趋势,但与对照组相比无显著性差异。结论: 急性臭氧暴露在较低浓度(0.12 ppm)时即可导致大鼠肺部细胞的DNA损伤;而在较高浓度(4 ppm)时却未见显著的染色体损伤。     

Chromosome aberrations and sister-chromatid exchange frequencies in pathology staff occupationally exposed to formaldehyde

Past studies have shown that formaldehyde is mutagenic in microbial tests and Drosophila and causes chromosomal aberrations in cultured mammalian cells. Chromosomal analysis of bone marrow cells and spermatocytes from exposed laboratory animals has failed to show any genotoxic effect. Information on individuals occupationally exposed is limited and there is no evidence to date that formaldehyde can induce chromosome damage at occupational levels of exposure. This study examines the chromosome aberration and sister-chromatid exchange frequencies in lymphocytes from a group of 6 pathology workers and 5 unexposed controls. No detectable differences could be found between the groups in either chromosomal aberration induction or sister-chromatid exchange frequencies.     

Effect of carnosine supplementation on apoptosis and irisin,total oxidant and antioxidants levels in the serum,liver and lung tissues in rats exposed to formaldehyde inhalation

The main objective of the study has been to show whether carnosine has positive effects on liver and lung tissues of rats exposed to a range of formaldehyde concentrations, and to explore how irisin expression and antioxidant capacity are altered in these tissues by carnosine supplementation. Sprague-Dawley type male rats were divided into 8 groups with 6 animals in each: (I) Control; no chemical supplementation); (II) sham (100 mg/kg/day carnosine); (III) low dose formaldehyde (LDFA) for 5 days/week; (IV) LDFA for 5 days/week and carnosine); (V) moderate dose formaldehyde (MDFA) for 5 days/week); (VI) MDFA for 5 days/week and carnosine; (VII) high dose formaldehyde (HDFA) for 5 days/week; (VIII) and HDFA for 5 days/week and carnosine. Sham and control groups were exposed to normal air. Irisin levels of the serum, liver and lung tissue supernatants were analyzed by ELISA, while the REL method was used to determine total oxidant/antioxidant capacity. Irisin production by the tissues was detected immunohistochemically. Increasing doses of FA decreased serum/tissue irisin and total antioxidant levels relative to the controls, as also to increases in TUNEL expressions, total oxidant level, oxidant and apoptosis index. Irisin expression was detected in hepatocyte and sinusoidal cells of the liver and parenchymal cells of the lung. In conclusion, while FA exposure reduces irisin and total oxidant in the serum, liver and lung tissues in a dose-dependent manner and increases the total antioxidant capacity, carnosine supplementation reduces the oxidative stress and restores the histopathological and biochemical signs.     

Vitellogenin in rare minnow (Gobiocypris rarus): identification and induction by waterborne diethylstilbestrol

Rare minnow (Gobiocypris rarus) is a tiny Chinese carp that has a short life cycle and is easily cultured in the laboratory. In this study, juvenile rare minnows were exposed to waterborne diethylstilbestrol (DES) at 0.05, 0.5 and 5 microg/l in laboratory aquaria. After exposure for 4, 8, 13 and 21 days, juvenile fish were collected and vitellogenin (Vtg) was measured in whole body homogenates. Native and SDS electrophoresis followed by Western blotting were performed for Vtg identification, and a non-competitive ELISA was developed. In the DES exposure groups (0.5 and 5 microg/l DES), Vtg appeared after 4 days, increased significantly after 8 days and reached a maximum on day 13. Further, a significant increase in the hepatosomatic index (HSI) was found in the 5 microg/l DES exposure group after 21 days. These results indicate that rare minnow provides a good model for assessing endocrine disruption by environmental estrogens.     

Time of the sidereal year affects responsiveness to the phase-resetting effects of photoperiod in the ewe

Two groups of ovary-intact ewes were placed in separate photochambers on the day of the vernal equinox (VE). One group was exposed to a 16 h light:8 h dark (16L:8D) photoperiod and the other to 8L:16D. On the day of the summer solstice (SS) and at 90-91-day intervals thereafter [autumnal equinox (AE), winter solstice (WS), VE and SS], each group was changed to the opposite photoperiod. The latent period between each change and either onset or cessation of cycles, as determined by measuring blood progesterone concentrations, was recorded. The latent period between change to 8L:16D and onset of cycles was shortest after the exposure at AE and longest after exposure at WS (P less than 0.001). The latent period after AE was shorter (P less than 0.001) than after VE. The correlations were small between ambient temperature and interval to onset of cycles. The latent period to cessation of cycles in response to 16L:8D was shorter after SS exposure than after WS exposure (P less than 0.01), but other differences were not significant. There was a strong (r = -0.94, P less than 0.05) negative correlation between interval to cessation of cycles and ambient temperature. Cessation of cycles in response to 16L:8D occurred more rapidly (P less than 0.001) than onset in response to 8L:16D. These results show that responsiveness to the inductive effects of photoperiod varies significantly with time of the sidereal year.     

Long-term enhancement of pulmonary gas exchange after high-altitude residence during maturation.

In a previous study, our laboratory showed that young dogs born at sea level (SL) and raised from 2.5 mo of age to beyond somatic maturity at a high altitude (HA) of 3,100 m show enhanced resting lung function (Johnson RL Jr, Cassidy SS, Grover RF, Schutte JE, and Epstein RH. J Appl Physiol 59: 1773-1782, 1985). To examine whether HA-induced adaptation improves pulmonary gas exchange during exercise and whether adaptation is reversible when animals return to SL before somatic maturity, we raised 2.5-mo-old foxhounds at HA (3,800 m) for 5 mo (to age 7.5 mo) before returning them to SL. Lung function was measured under anesthesia 1 mo and 2 yr after return to SL and during exercise approximately 1 yr after return. In animals exposed to HA relative to simultaneous litter-matched SL controls, resting circulating blood and erythrocyte volumes, lung volumes, septal volume estimated by a rebreathing technique, and lung tissue volume estimated by high-resolution computed tomography scan were persistently higher. Lung diffusing capacity, membrane diffusing capacity, and pulmonary capillary blood volume estimated at a given cardiac output were significantly higher in animals exposed to HA, whereas maximal oxygen uptake and hematocrit were similar between groups. We conclude that relatively short exposure to HA during somatic maturation improves long-term lung function into adulthood.     

Photoperiod affects reproductive responsiveness to 6-methoxy-2-benzoxazolinone in house mice

House mice (Mus musculus) have traditionally been characterized as nonphotoperiodic because reproductive function is unaffected by day length in the laboratory. In the present study, the reproductive responsiveness of CF1 mice to a naturally occurring plant metabolite was assessed in animals that were maintained in either long (16L:8D) or short (8L:16D) photoperiods from birth until the end of the study. Males and females were implanted i.p. with either an empty Silastic capsule or one containing 6-methoxy-2-benzoxazolinone (6-MBOA) at either 21 or 60 days of age for 3 days. Other 31-day-old mice were implanted with capsules for 8 wk. Three-day exposure to 6-MBOA stimulated uterine growth in short-day, adult females, but did not affect adult females housed in long photoperiods. Short-term treatment with 6-MBOA did not significantly affect reproductive parameters in either long- or short-day peripubertal house mice, or in adult males regardless of photoperiod, nor did exposure to 6-MBOA for 8 wk influence reproduction in males in either photoperiodic condition. However, short-day female mice had significantly reduced ovarian and uterine masses after 8 wk chronic 6-MBOA treatment as compared to long-day animals or mice unexposed to 6-MBOA. Short-day females exposed to 6-MBOA for 8 wk developed a denser pelage compared to long-day mice treated with this compound. Photoperiod-mediated differential responsiveness to 6-MBOA indicates that female house mice can discriminate long from short days, and these results suggest that the physiological mechanisms for photoperiodic responsiveness remain extant in this species previously characterized as nonphotperiodic.     

纳米炭黑颗粒复合寒冷暴露对小鼠肺部氧化应激反应的影响

目的：研究纳米炭黑颗粒复合寒冷暴露对小鼠肺部组织结构及其氧化应激反应的影响。方法：将72只健康雄性C57BL/6小鼠随机分为6组：对照（Ctrl）组、单纯冷暴露（C）组、低剂量染毒（L）组、低剂量染毒复合冷暴露（LC）组、高剂量染毒（H）组、高剂量染毒复合冷暴露（HC）组。采用吸入式气管滴注染毒方式,一次性滴注纳米炭墨颗粒染毒液40 μl,浓度分别为0.45 mg/ml （L）和4.05 mg/ml （H）。冷暴露方式为4℃暴露,4 h/d,连续20 d。暴露结束24 h后称重、取样,进行相关指标测定。采用试剂盒法测定小鼠肺组织匀浆中超氧化物歧化酶（SOD）活力、谷胱甘肽过氧化物酶（GSH-Px）活力和丙二醛（MDA）含量;肺组织块HE染色,观察肺组织病理组织结构改变。结果：所有冷暴露处理组小鼠的体重均显著低于所有非冷暴露组（P<0.05）,对照组及单纯染毒组小鼠体重均在实验开始14 d后明显升高（P<0.05）,单纯冷暴露组与纳米炭黑颗粒染毒复合冷暴露组小鼠体重均在14 d后趋于稳定。HE检测结果表明,单纯纳米炭黑颗粒染毒组及染毒复合冷暴露组小鼠肺泡腔内均有黑色颗粒沉积,高剂量染毒复合冷暴露组可见肺泡结构破环,排列凌乱,有大量炎细胞浸润。与对照组相比,其余各组SOD活力均显著降低（P<0.05）;高剂量染毒组及高剂量染毒复合冷暴露组GSH-Px活力明显低于对照组（P<0.01）;与对照组相比,高剂量染毒组、低剂量染毒与高剂量染毒复合冷暴露组MDA含量显著升高（P<0.01）。两因素方差分析提示,随着染毒剂量的增加,SOD活力及GSH-Px活力显著降低（P<0.05）;随着温度的降低,肺组织MDA含量显著升高（P<0.05）,4℃间歇性冷暴露与纳米颗粒物暴露对肺组织SOD、GSH-Px活力及MDA含量的影响均无交互作用。结论：纳米炭黑颗粒复合寒冷暴露可导致小鼠肺部炎症反应加重,氧化应激水平升高。