CCR2 monocytes as therapeutic targets for acute disc herniation and radiculopathy in mouse models.

OBJECTIVE: Back pain and radiculopathy caused by disc herniation are major health issues worldwide. While macrophages are key players in disc herniation induced inflammation, their roles and origins in disease progression remain unclear. We aim to study the roles of monocytes and derivatives in a mouse model of disc herniation. METHODS: Using a CCR2-CreER; R26R-EGFP (Ai6) transgenic mouse strain, we fate-mapped C-C chemokine receptor type 2 (CCR2) expressing monocytes and derivatives at disc herniation sites, and employed a CCR2RFP/RFP mouse strain and a CCR2-specific antagonist to study the effects of CCR2+ monocytes on local inflammatory responses, pain level, and disc degeneration by immunostaining, flow cytometry, and histology. RESULTS: CCR2+ monocytes (GFP+) increased at the sites of disc hernia over postoperative day 4, 6, and 9 in CCR2-CreER; Ai6 mice. F4/80+ cells increased, and meanwhile, CD11b+ cells trended downward. Co-localization analysis revealed that both GFP+CD11b+ and GFP+F4/80+ constituted the majority of CD11b+ and F4/80+ cells at disc hernia sites. Fluorescence activated cell sorter purified GFP+ cells exhibited higher cytokine expressions than GFP- cells. Inhibition of CCR2 signaling reduced infiltration of monocytes and macrophages, alleviated pain, maintained disc height, and reduced osteoclast activity in adjacent cortical bone for up to 1 month. CONCLUSION: Our findings suggest that circulating CCR2+ monocytes play important roles in initiating and promoting the local inflammatory responses, pain sensitization, and degenerative changes after disc herniation, and thus may serve as therapeutic targets for disc herniation induced back and leg pain.

Clinical Evaluation of an Antigen Home Test Using Surface-Enhanced Raman Spectroscopy and Stacking Pad for SARS-CoV-2 Screening with Nasal and Salivary Swab Samples.

This prospective study aimed to evaluate the performance of the InstaView COVID-19 (coronavirus diseases 2019) Antigen Home Test (InstaView AHT) which detects severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens. In this test kit, surface-enhanced Raman spectroscopy was used, a stacking pad was inserted, and nasal swab and salivary swab samples were used simultaneously to improve performance. The clinical performance of the InstaView AHT was compared to that of RT-PCR using nasopharyngeal samples. The participants without any prior training were recruited and performed the sample collection, testing, and interpretation of the results by themselves. Of the 91 PCR-positive patients, 85 had positive InstaView AHT results. The sensitivity and specificity of the InstaView AHT were 93.4% (95% confidence interval [CI]: 86.2-97.5) and 99.4% (95% CI: 98.2-99.9). The sensitivity of the InstaView AHT was above 90% for all samples obtained from patients with Ct ≤ 20, 20 < Ct ≤ 25, and 25 < Ct ≤ 30 (100%, 95.1%, and 92.0%, respectively). The InstaView AHT can be used as an alternative to RT-PCR testing because of its relatively high sensitivity and specificity, especially when SARS-CoV-2 prevalence is high, and the availability of RT-PCR testing is limited.

Outcomes Following Anterior Cervical Discectomy and Fusion in Patients With Ehlers-Danlos Syndrome.

STUDY DESIGN: Retrospective database analysis. OBJECTIVES: To study postoperative complication rates following anterior cervical discectomy and fusion (ACDF) in patients with Ehlers-Danlos syndrome (EDS) compared with patients without EDS. METHODS: The Mariner database was utilized to identify patients with EDS undergoing one or two level anterior cervical discectomy and fusion (ACDF). Postoperative short-term outcomes assessed included medical complications, readmissions, and ED-visits within 90 days of surgery. Additionally, surgical complications including wound complications, surgical site infection, one- and two-year anterior revision along with posterior revision, pseudarthrosis, and hardware failure within 2 years were assessed. Multivariate logistic regression was used to adjust for demographic variables, comorbidities and number of levels operated on. RESULTS: The present study identified 533 patients in the EDS group and 2634 patients in the matched control group. EDS patients undergoing ACDF are at an increased risk for 90-day major medical complications (OR 3.31; P < .001). EDS patients were also found to be associated with surgical complications including wound complications (OR 2.94; P < .001), surgical site infection (OR 8.60; P < .001) within 90 days, pseudarthrosis (OR 2.33; P < .001), instrument failure (OR 4.03; P < .001), anterior revision (OR 22.87; P < .001), and posterior revision (OR 3.17; P < .001) within 2 years. CONCLUSIONS: EDS is associated with higher rates of both medical and surgical complications following ACDF. Spine surgeons should be cognizant of the increased risks in this population to provide appropriate preoperative counseling and enhanced perioperative medical management.

Recent Advances in CAR-Based Solid Tumor Immunotherapy.

Adoptive cell therapy using chimeric antigen receptor (CAR) technology is one of the most advanced engineering platforms for cancer immunotherapy. CAR-T cells have shown remarkable efficacy in the treatment of hematological malignancies. However, their limitations in solid tumors include an immunosuppressive tumor microenvironment (TME), insufficient tumor infiltration, toxicity, and the absence of tumor-specific antigens. Although recent advances in CAR-T cell design-such as the incorporation of co-stimulatory domains and the development of armored CAR-T cells-have shown promising results in treating solid tumors, there are still challenges that need to be addressed. To overcome these limitations, other immune cells, such as natural killer (NK) cells and macrophages (M), have been developed as attractive options for efficient cancer immunotherapy of solid tumors. CAR-NK cells exhibit substantial clinical improvements with "off-the-shelf" availability and low toxicity. CAR-M cells have promising therapeutic potential because macrophages can infiltrate the TME of solid tumors. Here, we review the recent advances and future perspectives associated with engineered immune cell-based cancer immunotherapies for solid tumors. We also summarize ongoing clinical trials investigating the safety and efficacy of engineered immune cells, such as CAR-T, CAR-NK, and CAR-M, for targeting solid tumors.

Korea National Survey for Environmental Pollutants in the human body 2008: 1-hydroxypyrene, 2-naphthol, and cotinine in urine of the Korean population.

The Korea National Survey for Environmental Pollutants in the human body conducts representative Korean population studies, which were first initiated in 2005 in Korea. This study was conducted from 2008 to 2009 to determine the exposure levels of polycyclic aromatic hydrocarbons and nicotine in the Korean general population. The study population consisted of 4702 adult subjects from 196 sampling locations including coastal, rural, and urban areas. The urinary levels of 1-hydroxypyrene, 2-naphthol, and cotinine were measured for exposure of polycyclic aromatic hydrocarbons and nicotine. The geometric means of the urinary 1-hydroxypyrene, 2-naphthol and cotinine concentrations in the Korean general population were 0.15 µg/L (95% confidence interval (CI): 0.13-0.17), 3.84 µg/L (95% CI: 3.57-4.11) and 47.42 µg/L (95% CI: 40.52-54.32) respectively. When these values were compared with reference ranges for the United States and Germany, the levels of 1-hydroxypyrene, 2-naphthol, and cotinine were very similar for Korea and Germany, however, these levels were slightly lower in the United States. This study is the first nationwide survey of exposure to polycyclic aromatic hydrocarbons and nicotine in Korea and provides a background reference range for exposure to polycyclic aromatic hydrocarbons and nicotine in the Korean general population.

Subacute inhalation toxicity assessment of fly ash from industrial waste incinerators.

Fly ash from industrial waste incinerators has been a significant concern because of their constituent toxic heavy metals and organic compounds. The objective of this study was to identify the subacute inhalation toxicity of fly ash from industrial waste incinerators, using whole body inhalation exposure chambers. Male and female groups of Sprague-Dawley rats were exposed to fly ash by inhalation of concentrations of 0, 50, 100, 200 mg/m(3), for 6 h/day, 5 days/week for 4 weeks. There was no significant difference in body weight, and relative organ weight to body weight, between the exposure groups and the control group. Hematological examinations revealed a significant increase of monocyte counts in fly ash exposed rats and brown pigment laden macrophage was found in the lungs of rats exposed to high concentration of fly ash. A decrease of blood glucose levels and an increase in glutamate oxaloacetate transaminase activity were observed in fly ash treated rats. There was also a significant increase of lactate dehydrogenase levels in rat blood exposed fly ash. A significant dose-dependent increase of DNA damage was found in lymphocytes, spleen, bronchoalveolar lavage, liver, lung, and thymus of rats exposed to fly ash. In addition, the level of lipid peroxidation was increased in the plasma of rats exposed to a high concentration of fly ash. These results suggest that inhalation of fly ash from industrial waste incinerators can induce histopathologic, hematological, and serum biochemical changes and oxidative damage.

Molecular responses of Jurkat T-cells to 1763 MHz radiofrequency radiation.

PURPOSE: The biological effects of exposure to mobile phone emitted radiofrequency (RF) radiation are the subject of intense study, yet the hypothesis that RF exposure is a potential health hazard remains controversial. In this paper, we monitored cellular and molecular changes in Jurkat human T lymphoma cells after irradiating with 1763 MHz RF radiation to understand the effect on RF radiation in immune cells. MATERIALS AND METHODS: Jurkat T-cells were exposed to RF radiation to assess the effects on cell proliferation, cell cycle progression, DNA damage and gene expression. Jurkat cells were exposed to 1763 MHz RF radiation at 10 W/kg specific absorption rate (SAR) and compared to sham exposed cells. RESULTS: RF exposure did not produce significant changes in cell numbers, cell cycle distributions, or levels of DNA damage. In genome-wide analysis of gene expressions, there were no genes changed more than two-fold upon RF-radiation while ten genes change to 1.3 approximately 1.8-fold. Among ten genes, two cytokine receptor genes such as chemokine (C-X-C motif) receptor 3 (CXCR3) and interleukin 1 receptor, type II (IL1R2) were down-regulated upon RF radiation, but they were not directly related to cell proliferation or DNA damage responses. CONCLUSION: These results indicate that the alterations in cell proliferation, cell cycle progression, DNA integrity or global gene expression was not detected upon 1763 MHz RF radiation under 10 W/kg SAR for 24 h to Jurkat T cells.

Characterization of biological effect of 1763 MHz radiofrequency exposure on auditory hair cells.

PURPOSE: Radiofrequency (RF) exposure at the frequency of mobile phones has been reported not to induce cellular damage in in vitro and in vivo models. We chose HEI-OC1 immortalized mouse auditory hair cells to characterize the cellular response to 1763 MHz RF exposure, because auditory cells could be exposed to mobile phone frequencies. MATERIALS AND METHODS: Cells were exposed to 1763 MHz RF at a 20 W/kg specific absorption rate (SAR) in a code division multiple access (CDMA) exposure chamber for 24 and 48 h to check for changes in cell cycle, DNA damage, stress response, and gene expression. RESULTS: Neither of cell cycle changes nor DNA damage was detected in RF-exposed cells. The expression of heat shock proteins (HSP) and the phosphorylation of mitogen-activated protein kinases (MAPK) did not change, either. We tried to identify any alteration in gene expression using microarrays. Using the Applied Biosystems 1700 full genome expression mouse microarray, we found that only 29 genes (0.09% of total genes examined) were changed by more than 1.5-fold on RF exposure. CONCLUSION: From these results, we could not find any evidence of the induction of cellular responses, including cell cycle distribution, DNA damage, stress response and gene expression, after 1763 MHz RF exposure at an SAR of 20 W/kg in HEI-OC1 auditory hair cells.

Panax ginseng effects on DNA damage, CYP1A1 expression and histopathological changes in testes of rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The effects of Panax ginseng extracts on DNA damage, expression of cytochrome P450 (CYP) 1A1 and reproductive toxicity were evaluated in the testis of rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxinthe (TCDD). Fifty rats were divided into five groups according to treatment with 2,3,7,8-TCDD and P. ginseng extracts. Single cell gel electrophoresis assays were performed to evaluate DNA damage that occurred in the lymphocytes of rats. Histological changes in the seminiferous tubules of the testis were determined using Johnsen's scoring system and Real Time-PCR was performed to evaluate the mRNA expression of CYP1A1. Significant pathological effects were observed in the 2,3,7,8-TCDD treated rats including a reduced seminiferous tubular diameter, an increased number of damaged tubules (maturation arrest, eosinophilic degeneration and spermatid giant cells) and increased Johnsen's score. DNA damage and the expression of CYP1A1 mRNA were significantly increased in rat testes. There were no significant differences between the control and animals treated with P. ginseng extracts. However, a significantly decreased level of DNA damage, decreased CYP1A1 expression and reduced pathological effects were observed in the 2,3,7,8-TCDD with P. ginseng extracts treated groups when compared with the TCDD treated group. In summary, our study demonstrates that 2,3,7,8-TCDD induces the pathological and genotoxical damage in rat testes, while P. ginseng extract treatment exhibits a therapeutic capacity to reduce these effects via reduction of CYP1A1 mRNA.

Oxidative damages in the DNA, lipids, and proteins of rats exposed to isofluranes and alcohols.

DNA damage, lipid peroxidation and protein oxidation were evaluated in rats exposed to a 1% isoflurane atmosphere with or without alcohol administration (administrated by gastric intubation at 4 g/kg body weight as a 50% solution). Single cell gel electrophoresis assays were performed in order to evaluate DNA damage occurring in the lymphocytes, spleen, bone marrow, brain, livers and lung of rats exposed to 1% isoflurane for 30 or 60 min with/without ethanol. Levels of malondialdehydes (MDA), a metabolite of lipid peroxidation, were determined in plasma and tissues. Carbonyl contents were also analyzed to determine levels of protein oxidation in plasma and tissues. Levels of DNA damage in lymphocytes, bone marrow, and the organ tissues of rats exposed to isoflurane were found to increase time dependently, and alcohol increased DNA damage. Lipid peroxidation and protein oxidation results showed patterns that differed from those of DNA damage. Levels of MDA in plasma, bone marrow, spleen, and the livers of rats exposed to isoflurane with/without ethanol were found to be time dependently increased, but this was not observed in the brain or lung. However, protein oxidation levels were significantly increased in the plasma, brains, and lungs of rats exposed to isoflurane, and exposure to isoflurane and alcohol, significantly increased these levels in plasma and brain. The present study demonstrates that isoflurane exposure results in significant DNA damage in rat lymphocytes, bone marrow, spleen, brain, livers, and lung. Moreover, alcohol was found to be as a strong inducer of DNA damage, lipid peroxidation and protein oxidation. However, no evidence in association between DNA damage, lipid peroxidation and protein oxidation was found. Regarding the effects of isoflurane and alcohol on oxidative damages, single strand DNA damages may be a useful biomarkers and blood cells and plasma appear to be more sensitive targets to oxidative damage than other tissues.

Comparison of immunnological and genotoxicological parameters in automobile emission inspectors exposed to polycyclic aromatic hydrocarbons.

In this study, we investigated the immunotoxicities of polycyclic aromatic hydrocarbons in 54 automobile emission inspectors and in 84 control subjects, and evaluated associations between immunological and genotoxicological parameters. Specific surface antigens of peripheral lymphocytes, namely, CD3, CD4, CD8, CD19, and CD69 were subjected to measure immune status in automobile emission inspectors and control subjects. T-and B-cells showed no significant differences between automobile emission inspectors and control subjects (p=0.740 and 0.395). In addition, the ratio of T helper cells to T cytotoxic cells was not deferent (p=0.144). However, T-cell activation was found to be significantly higher in automobile emission inspectors (p=0.041), but not B-cell activation. The levels of two cytokines (IL-4 an INF-γ) and four immunoglobulins (IgA, IgE, IgG, and IgM) were also determined in automobile emission inspectors and control subjects. All immunoglobulin types were lower in automobile emission inspectors, but this was significant only for IgG (0.047). In addition, the levels of two cytokines, IL-4 and INF-γ, were also higher in automobile emission inspectors, though this was not significant. DNA damage in mononuclear and polynuclear lymphocytes and in the level of urinary metabolites, 1-OHP and 2-naphthol, were evaluated in automobile emission inspectors and in control subjects and significant differences were found between the two groups. Examinations of urinary metabolites, DNA damage, and immunological parameters, including leukocyte subpopulations, immunoglobulins, and cytokines, showed that the cytokines levels were associated with the levels of two urinary metabolites, 1-OHP and 2-naphthol.

Evaluation of immuno- and reproductive toxicities and association between immunotoxicological and genotoxicological parameters in waste incineration workers.

In this study, we investigated immunotoxicity levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin in 31 waste incineration workers and in 84 control subjects, and evaluated the association between immunological and genotoxicological parameters. DNA damage in mononuclear and polynuclear lymphocytes, and the level of the urinary metabolites, 1-OHP and 2-naphthol, were evaluated in both waste incineration workers and control subjects. Significant differences were detected in these values between exposed and control groups. Number of sperms was lower in the waste incineration workers than in the control subjects, as was the percentage of motile sperms, but a significant difference existed only in the number of sperms (p=0.05). DNA damage in the spermatozoa of waste incineration workers and control subjects measured 1.40+/-0.08 and 1.26+/-0.03, respectively (p=0.001). Specific surface antigens of peripheral lymphocytes, namely, CD3, CD4, CD8, CD19, and CD69 were used to measure immune status in waste incineration workers and control subjects. There was no significant difference in T- and B-cell profiles showed between waste incineration workers and control subjects (p=0.684 and 0.157). In addition, the ratio of T helper cells to T cytotoxic cells was also not remarkably different between groups (p=0.174). However, T-cell activation was found to be significantly higher in the waste incineration workers than in the control subjects (p=0.001), although B-cell activation did not exhibit this trend. The levels of two cytokines (IL-4 an INF-gamma) and four immunoglobulins (IgA, IgE, IgG, and IgM) were also measured in the experimental population. All immunoglobulin types were found in lower amounts in the waste incineration workers, but this diaparity was not significant one. In addition, the levels of two cytokines, IL-4 and INF-gamma, were also found to be lower in the waste incineration workers than in the control subjects, and only in IL-4 was a significant difference determined to exist.

DNA damage in lymphocytes of benzene exposed workers correlates with trans,trans-muconic acids and breath benzene levels.

Benzene causes many kinds of blood disorders in workers employed in many different environments. These diseases include myelodisplastic syndrome and acute and chronic myelocytic leukemia. In the present study, five occupational work places, including six industrial process types, namely, printing, shoe-making, methylene di-aniline (MDA), nitrobenzene, carbomer, and benzene production were selected, and the levels of breath benzene, and trans,trans-muconic acids (t,t-MA) and phenol in urine were evaluated, as well as hematological changes and lymphocyte DNA damage. The concentration of benzene in breath was less than 3 ppm in the workplaces, and benzene exposure was found to be higher in work places where benzene is used, than in those where benzene is produced. At low levels of benzene exposure, urinary t,t-MA correlated strongly with benzene in air. Highest Olive tail moments were found in workers producing carbomer. Levels of breathzone benzene were found to be strongly correlated with Olive tail moment values in the lymphocytes of workers, but not with hematological data in the six workplaces types. In conclusion, the highest benzene exposures found occurred in workers at a company, which utilized benzene in the production of carbomer. In terms of low levels of exposure to benzene, urinary t,t-MA and DNA damage exhibited a strong correlation with breath benzene, but not with hematological data. We conclude that breath benzene, t,t-MA and lymphocytic DNA damage are satisfactory biomonitoring markers with respect to benzene exposure in the workplace.

Evaluation of biological monitoring markers using genomic and proteomic analysis for automobile emission inspectors and waste incinerating workers exposed to polycyclic aromatic hydrocarbons or 2,3,7,8,-tetracholrodedibenzo-p-dioxins.

In this study, we investigated the effects of PAHs and dioxin on mRNA and plasma protein expression using genomic and proteomic analysis for automobile emission inspectors and waste incineration workers. About 54 workers from automobile emission inspection offices, 31 workers from waste incinerating company and 84 unexposed healthy subjects were enrolled in this study. Urine and air samples were collected and analyzed by HPLC and GC/MS. Comet assays were carried out to evaluate any DNA damage in mononuclear and polynuclear cells. A significant difference in Olive tail moments in mononuclear cells was observed between exposed and control subjects (P < 0.0001). To examine the differences of the gene expression profile in automobile emission inspectors and waste incineration workers, radioactive complementary DNA microarrays were used to evaluate changes in the expression of 1,152 total genes. The gene expression profiles showed that 11 genes were up-regulated and 4 genes were down-regulated in waste incinerating workers as compared with controls. Plasma proteins were analyzed by 2-dimentional electrophoresis with pH 3-10 NL IPG Dry strip. The protein expression profiles showed that 8 proteins were up- regulated and 1 protein, haptoglobin, was down- regulated in automobile emission inspectors and waste incineration workers. Serum paraoxonase/ arylesterase was found only in the plasma of waste incineration workers. The expression of genes and proteins involved in oxidative stress were up-regulated in both automobile emission inspectors and waste incineration workers. Several proteins, such as transthyrethin, sarcolectin and haptoglobin, that were highly up- or down-regulated, could serve as biological monitoring markers for future study.

Use of the tail moment of the lymphocytes to evaluate DNA damage in human biomonitoring studies.

The Comet assay has gained increasing popularity for use in human biomonitoring or epidemiologic studies; however, one of the shortcomings of the Comet assay is a lack of agreement on a single appropriate Comet parameter that is capable of adequately describing observed DNA damages. Among the tail parameters of Comet features, the most frequently used are the tail moments (both the Olive tail moment and the extent tail moment), the tail DNA, and the tail length. Some studies comparing Comet parameters have been found in cell toxicity research, but there are few comparative studies that use human biomonitoring or epidemiologic data. In this study, we evaluate those four tail parameters in both high and low DNA damaged cells with the use of epidemiologic data. To do this, a new graphical approach, the so-called quantile dispersion graphs (QDGs) are used. In a comparison of an exposed group and a control group, either the tail moment or tail DNA is preferable to the tail length. With respect to providing smaller variability in quantiles for the amount of DNA damage, however, the tail moment is the preferred parameter for both groups. Moreover, the tail moment provides the most stable estimates for DNA damage because it has a larger degree of uniformity in quantile dispersions. To study high degrees of damage from toxic exposure using B cells or G cells, however, the tail DNA showed more significant discrepancies than the other parameters, in terms of both the mean differences and the graphical differences between the two groups. In view of this result, it is suggested that both the tail moment and the tail DNA be presented as tail parameters in human biomonitoring studies.

Single strand DNA breaks in T- and B-lymphocytes and granulocytes in workers exposed to benzene.

Comet assays were carried out to evaluate DNA damage in T- and B-lymphocytes and granulocytes from 41 workers exposed to benzene in a printing company and 41 unexposed donors. In T-lymphocytes, DNA damage was slightly higher in exposed workers than in controls. The tail moments in the two groups were 1.75+/-0.29 and 1.47+/-0.41, respectively (P<0.0006). DNA damage of B-lymphocytes in the two groups showed the most significant difference among the three cell types. The tail moments were 3.86+/-0.71 and 1.51+/-0.39, respectively (P<0.0001). In granulocytes, DNA damage was also different, the tail moments being 3.61+/-0.75 and 2.60+/-0.59, respectively (P<0.0001). The comparison of DNA damage in both groups shows that B-lymphocytes could be a useful target in biomonitoring of human exposure to low levels of benzene.

DNA damage in T- and B-lymphocytes and granulocytes in emission inspection and incineration workers exposed to polycyclic aromatic hydrocarbons.

In this study, we investigated by using comet assay the effects of polycyclic aromatic hydrocarbon (PAH) as a major factor on DNA damage of workers exposed to exhaust fumes. Twenty-four workers from three automobile emission inspection companies, 28 workers from a waste incinerating company, and 43 matched, unexposed healthy subjects were enrolled in the study. The mean values of 1-hydroxypyrene (1-OHP) in automobile emission inspection and waste incineration workers were 0.27+/-0.19 and 0.57+/-0.46 micromol/mol creatinine, respectively, and the mean values of 2-naphthol in automobile emission inspectors and waste incineration workers were 4.80+/-4.01 and 8.30+/-4.79 mol/mol creatinine, respectively. Significant difference in urinary metabolites, 1-hydroxypyrene and 2-naphthol was found between smokers and non-smokers in exposed groups and it may be due to the amounts of smoking cigarettes. In T-lymphocytes, DNA damage in control subjects, emission inspection workers and incineration workers were 1.42+/-0.22, 1.41+/-0.22 and 1.76+/-0.27, respectively. DNA damage of B-lymphocytes in the three groups showed the most significant differences of three cell types. The tail moments of the B-lymphocytes of control subjects, emission inspection and incineration workers were 1.40+/-0.27, 2.44+/-0.32 and 2.36+/-0.37, respectively. In granulocytes, DNA damage was also different, the tail moments being 2.72+/-0.59, 3.32+/-0.38 and 2.85+/-0.49, respectively. Although 1-OHP and 2-naphthol levels were statistically increased in smokers in workers exposed to PAHs, exposed smoking and non-smoking workers did not show any significantly difference in terms of Olive tail moments. Our results suggest that PAH causes single strand DNA breakage in human T- and B-lymphocytes, and granulocytes. A comparison of DNA damage in three groups showed that B-lymphocytes are useful target in the biomonitoring of human exposure.

Effects of hair dyeing on DNA damage in human lymphocytes.

Comet assays were carried out to evaluate DNA damage in human lymphocytes from 20 volunteers before and after hair dyeing. DNA damage in lymphocytes was found to be slightly higher in volunteers after hair dyeing. Tail moments before and after hair dyeing were 1.47 +/- 0.41 and 1.75 +/- 0.29 respectively (p<0.0008). DNA damage in lymphocytes showed significant difference with treatment and heating time. The tail moments after 15 min of treatment time before and after hair dyeing were 1.44 +/- 0.22 and 1.85 +/- 0.36, respectively (p=0.0004) and the corresponding tail moments in 20 min of heating time before and after were 1.37 +/- 0.15 and 1.78 +/- 0.34 (p=0.0002). In conclusion, we found that an acute exposure of hair dyes with heating caused DNA damages in peripheral lymphocytes and that this damage had significant association with treatment and heating time.

Inhalation exposure to chloramine T induces DNA damage and inflammation in lung of Sprague-Dawley rats.

Chloramine T has been widely used as a disinfectant in many areas such as kitchens, laboratories and hospitals. It has been also used as a biocide in air fresheners and deodorants which are consumer products; however, little is known about its toxic effects by inhalation route. This study was performed to identify the subacute inhalation toxicity of chloramine T under whole-body inhalation exposure conditions. Male and female groups of rats were exposed to chloramine T at concentrations of 0.2, 0.9 and 4.0 mg/m³ for 6 hr/day, 5 days/week during 4 weeks. After 28-day repeated inhalation of chloramine T, there were dose-dependently significant DNA damage in the rat tissues evaluated and inflammation was histopathologically noted around the terminal airways of the lung in both genders. As a result of the expression of three types of antioxidant enzymes (SOD-2, GPx-1, PRX-1) in rat's lung after exposure, there was no significant change of all antioxidant enzymes in the male and female rats. The results showed that no observed adverse effect level (NOAEL) was 0.2 mg/m³ in male rats and 0.9 mg/m³ in female rats under the present experimental condition.

Differential gene expression profiles in spontaneously hypertensive rats induced by administration of enalapril and nifedipine.

Enalapril and nifedipine are used as antihypertensive drugs; however, the therapeutic target molecules regulated by enalapril and nifedipine have yet to be fully identified. The aim of this study was to identify novel target genes that are specifically regulated by enalapril and nifedipine in tissues from spontaneously hypertensive rats (SHR) using DNA microarray analysis. We found that administration of SHR with enalapril and nifedipine differentially regulated 33 genes involved in the pathogenesis of cardiovascular diseases. Furthermore, we identified 16 genes that have not previously been implicated in cardiovascular diseases, including interleukin-24 (IL-24). Among them, exogenous administration of IL-24 attenuated the expression of vascular inflammation and hypertension-related genes induced by H2O2 treatment in mouse vascular smooth muscle (MOVAS) cells. This study provides valuable information for the development of novel antihypertensive drugs. In addition, the genes identified may be of use as biomarkers and therapeutic targets for cardiovascular diseases, including hypertension.