Bean Chen - Academia.edu (original) (raw)
Papers by Bean Chen
Particle and fibre toxicology, 2014
Engineered carbon nanotubes are currently used in many consumer and industrial products such as p... more Engineered carbon nanotubes are currently used in many consumer and industrial products such as paints, sunscreens, cosmetics, toiletries, electronic processes and industrial lubricants. Carbon nanotubes are among the more widely used nanoparticles and come in two major commercial forms, single-walled carbon nanotubes (SWCNT) and the more rigid, multi-walled carbon nanotubes (MWCNT). The low density and small size of these particles makes respiratory exposures likely. Many of the potential health hazards have not been investigated, including their potential for carcinogenicity. We, therefore, utilized a two stage initiation/promotion protocol to determine whether inhaled MWCNT act as a complete carcinogen and/or promote the growth of cells with existing DNA damage. Six week old, male, B6C3F1 mice received a single intraperitoneal (ip) injection of either the initiator methylcholanthrene(MCA, 10 μg/g BW, i.p.), or vehicle (corn oil). One week after i.p. injections, mice were exposed ...
Journal of Applied Toxicology, 2013
Identification of molecular target(s) and mechanism(s) of silica-induced pulmonary toxicity is im... more Identification of molecular target(s) and mechanism(s) of silica-induced pulmonary toxicity is important for the intervention and/or prevention of diseases associated with exposure to silica. Rats were exposed to crystalline silica by inhalation (15 mg m(-3), 6 h per day, 5 days) and global gene expression profile was determined in the lungs by microarray analysis at 1, 2, 4, 8 and 16 weeks following termination of silica exposure. The number of significantly differentially expressed genes (>1.5-fold change and <0.01 false discovery rate P-value) detected in the lungs during the post-exposure time intervals analyzed exhibited a steady increase in parallel with the progression of silica-induced pulmonary toxicity noticed in the rats. Quantitative real-time PCR analysis of a representative set of 10 genes confirmed the microarray findings. The number of biological functions, canonical pathways and molecular networks significantly affected by silica exposure, as identified by the bioinformatics analysis of the significantly differentially expressed genes detected during the post-exposure time intervals, also exhibited a steady increase similar to the silica-induced pulmonary toxicity. Genes involved in oxidative stress, inflammation, respiratory diseases, cancer, and tissue remodeling and fibrosis were significantly differentially expressed in the rat lungs; however, unresolved inflammation was the single most significant biological response to pulmonary exposure to silica. Excessive mucus production, as implicated by significant overexpression of the pendrin coding gene, SLC26A4, was identified as a potential novel mechanism for silica-induced pulmonary toxicity. Collectively, the findings of our study provided insights into the molecular mechanisms underlying the progression of crystalline silica-induced pulmonary toxicity in the rat. Published 2012. This article is a US Government work and is in the public domain in the USA.
Toxicological Sciences, 2011
Blood gene expression profiling was investigated as a minimally invasive surrogate approach to de... more Blood gene expression profiling was investigated as a minimally invasive surrogate approach to detect silica exposure and resulting pulmonary toxicity. Rats were exposed by inhalation to crystalline silica (15 mg/m³, 6 h/day, 5 days), and pulmonary damage and blood gene expression profiles were determined after latency periods (0-16 weeks). Silica exposure resulted in pulmonary toxicity as evidenced by histological and biochemical changes in the lungs. The number of significantly differentially expressed genes in the blood, identified by microarray analysis, correlated with the severity of silica-induced pulmonary toxicity. Functional analysis of the differentially expressed genes identified activation of inflammatory response as the major biological signal. Induction of pulmonary inflammation, as suggested by the blood gene expression data, was supported by significant increases in the number of macrophages and infiltrating neutrophils as well as the activity of pro-inflammatory chemokines observed in the lungs of the silica-exposed rats. A gene expression signature developed using the blood gene expression data predicted the exposure of rats to lower, minimally toxic and nontoxic concentrations of silica. Taken together, our findings suggest the potential application of peripheral blood gene expression profiling as a minimally invasive surrogate approach to detect pulmonary toxicity induced by silica in the rat. However, further research is required to determine the potential application of our findings specifically to monitor human exposure to silica and the resulting pulmonary effects.
Journal of Aerosol Science
ABSTRACT
Inhalation Toxicology
... B. T. Chen, WE Bechtold, E. B. Barr, Y.4. Cheng, J. 1. Mauderly, and RG Cuddihy Inhalation To... more ... B. T. Chen, WE Bechtold, E. B. Barr, Y.4. Cheng, J. 1. Mauderly, and RG Cuddihy Inhalation Toxicology Research Institute, Lovelace Biomedical ... in cylindrical nose-only exposure tubes, have been exposed either inter-mittently (puff-by-puff), to smoke and fresh air (Kendrick et al ...
Aerosol Science and Technology
In indoor and mining environments, deposition or plate-out'' of radon progeny onto wall... more In indoor and mining environments, deposition or plate-out'' of radon progeny onto walls occurs simultaneously with attachment of the radon progeny to airborne particles. Attachment and plate-out processes affect the atmosphere in which radon exposures takes place by reducing concentrations and shifting activity size distributions. Both processes have important consequences in determining the deposition pattern and initial dose of inhaled radon progeny. Theoretical deposition models show that turbulence and natural convection in a room are the major factors that influence plate-out rates. Here we describe plate-out measurements for radon progeny and aerosol particles in a spherical chamber under controlled laboratory conditions. The temperature and velocity profiles in still and turbulent air were monitored. A 161-liter spherical aluminum chamber was used to study the mixing. During mixing, air velocity was detected when rotational speeds were higher than 500 rpm. Monodisperse silver aerosols and polystyrene latex particles in the size range of 5 nm to 2 μm were used in the deposition study. Radon-220 progeny were generated by passing Rn-220 gas into the chamber and letting the gas decay into ²¹²Pb. The deposition rates of the particles and radon progeny (²¹²Pb) in the chamber were determined by monitoring the concentration decay of the aerosol as a function of time.
Occupational and Environmental Medicine
To investigate the risk of silicosis among tin miners and to investigate the relation between sil... more To investigate the risk of silicosis among tin miners and to investigate the relation between silicosis and cumulative exposure to dust (Chinese total dust and respirable crystalline silica dust). A cohort study of 3010 miners exposed to silica dust and employed for at least 1 year during 1960-5 in any of four Chinese tin mines was conducted. Historical total dust data from China were used to create a job exposure matrix for facility, job title, and calendar year. The total dust exposure data from China were converted to estimates of exposure to respirable crystalline silica for comparison with findings from other epidemiological studies of silicosis. Each worker's work history was abstracted from the complete employment records in mine files. Diagnoses of silicosis were based on 1986 Chinese pneumoconiosis Roentgen diagnostic criteria, which classified silicosis as stages I-III-similar to an International Labour Organisation (ILO) classification of 1/1 or greater. There were 10...
Particle and fibre toxicology, 2014
Engineered carbon nanotubes are currently used in many consumer and industrial products such as p... more Engineered carbon nanotubes are currently used in many consumer and industrial products such as paints, sunscreens, cosmetics, toiletries, electronic processes and industrial lubricants. Carbon nanotubes are among the more widely used nanoparticles and come in two major commercial forms, single-walled carbon nanotubes (SWCNT) and the more rigid, multi-walled carbon nanotubes (MWCNT). The low density and small size of these particles makes respiratory exposures likely. Many of the potential health hazards have not been investigated, including their potential for carcinogenicity. We, therefore, utilized a two stage initiation/promotion protocol to determine whether inhaled MWCNT act as a complete carcinogen and/or promote the growth of cells with existing DNA damage. Six week old, male, B6C3F1 mice received a single intraperitoneal (ip) injection of either the initiator methylcholanthrene(MCA, 10 μg/g BW, i.p.), or vehicle (corn oil). One week after i.p. injections, mice were exposed ...
Journal of Applied Toxicology, 2013
Identification of molecular target(s) and mechanism(s) of silica-induced pulmonary toxicity is im... more Identification of molecular target(s) and mechanism(s) of silica-induced pulmonary toxicity is important for the intervention and/or prevention of diseases associated with exposure to silica. Rats were exposed to crystalline silica by inhalation (15 mg m(-3), 6 h per day, 5 days) and global gene expression profile was determined in the lungs by microarray analysis at 1, 2, 4, 8 and 16 weeks following termination of silica exposure. The number of significantly differentially expressed genes (>1.5-fold change and <0.01 false discovery rate P-value) detected in the lungs during the post-exposure time intervals analyzed exhibited a steady increase in parallel with the progression of silica-induced pulmonary toxicity noticed in the rats. Quantitative real-time PCR analysis of a representative set of 10 genes confirmed the microarray findings. The number of biological functions, canonical pathways and molecular networks significantly affected by silica exposure, as identified by the bioinformatics analysis of the significantly differentially expressed genes detected during the post-exposure time intervals, also exhibited a steady increase similar to the silica-induced pulmonary toxicity. Genes involved in oxidative stress, inflammation, respiratory diseases, cancer, and tissue remodeling and fibrosis were significantly differentially expressed in the rat lungs; however, unresolved inflammation was the single most significant biological response to pulmonary exposure to silica. Excessive mucus production, as implicated by significant overexpression of the pendrin coding gene, SLC26A4, was identified as a potential novel mechanism for silica-induced pulmonary toxicity. Collectively, the findings of our study provided insights into the molecular mechanisms underlying the progression of crystalline silica-induced pulmonary toxicity in the rat. Published 2012. This article is a US Government work and is in the public domain in the USA.
Toxicological Sciences, 2011
Blood gene expression profiling was investigated as a minimally invasive surrogate approach to de... more Blood gene expression profiling was investigated as a minimally invasive surrogate approach to detect silica exposure and resulting pulmonary toxicity. Rats were exposed by inhalation to crystalline silica (15 mg/m³, 6 h/day, 5 days), and pulmonary damage and blood gene expression profiles were determined after latency periods (0-16 weeks). Silica exposure resulted in pulmonary toxicity as evidenced by histological and biochemical changes in the lungs. The number of significantly differentially expressed genes in the blood, identified by microarray analysis, correlated with the severity of silica-induced pulmonary toxicity. Functional analysis of the differentially expressed genes identified activation of inflammatory response as the major biological signal. Induction of pulmonary inflammation, as suggested by the blood gene expression data, was supported by significant increases in the number of macrophages and infiltrating neutrophils as well as the activity of pro-inflammatory chemokines observed in the lungs of the silica-exposed rats. A gene expression signature developed using the blood gene expression data predicted the exposure of rats to lower, minimally toxic and nontoxic concentrations of silica. Taken together, our findings suggest the potential application of peripheral blood gene expression profiling as a minimally invasive surrogate approach to detect pulmonary toxicity induced by silica in the rat. However, further research is required to determine the potential application of our findings specifically to monitor human exposure to silica and the resulting pulmonary effects.
Journal of Aerosol Science
ABSTRACT
Inhalation Toxicology
... B. T. Chen, WE Bechtold, E. B. Barr, Y.4. Cheng, J. 1. Mauderly, and RG Cuddihy Inhalation To... more ... B. T. Chen, WE Bechtold, E. B. Barr, Y.4. Cheng, J. 1. Mauderly, and RG Cuddihy Inhalation Toxicology Research Institute, Lovelace Biomedical ... in cylindrical nose-only exposure tubes, have been exposed either inter-mittently (puff-by-puff), to smoke and fresh air (Kendrick et al ...
Aerosol Science and Technology
In indoor and mining environments, deposition or plate-out'' of radon progeny onto wall... more In indoor and mining environments, deposition or plate-out'' of radon progeny onto walls occurs simultaneously with attachment of the radon progeny to airborne particles. Attachment and plate-out processes affect the atmosphere in which radon exposures takes place by reducing concentrations and shifting activity size distributions. Both processes have important consequences in determining the deposition pattern and initial dose of inhaled radon progeny. Theoretical deposition models show that turbulence and natural convection in a room are the major factors that influence plate-out rates. Here we describe plate-out measurements for radon progeny and aerosol particles in a spherical chamber under controlled laboratory conditions. The temperature and velocity profiles in still and turbulent air were monitored. A 161-liter spherical aluminum chamber was used to study the mixing. During mixing, air velocity was detected when rotational speeds were higher than 500 rpm. Monodisperse silver aerosols and polystyrene latex particles in the size range of 5 nm to 2 μm were used in the deposition study. Radon-220 progeny were generated by passing Rn-220 gas into the chamber and letting the gas decay into ²¹²Pb. The deposition rates of the particles and radon progeny (²¹²Pb) in the chamber were determined by monitoring the concentration decay of the aerosol as a function of time.
Occupational and Environmental Medicine
To investigate the risk of silicosis among tin miners and to investigate the relation between sil... more To investigate the risk of silicosis among tin miners and to investigate the relation between silicosis and cumulative exposure to dust (Chinese total dust and respirable crystalline silica dust). A cohort study of 3010 miners exposed to silica dust and employed for at least 1 year during 1960-5 in any of four Chinese tin mines was conducted. Historical total dust data from China were used to create a job exposure matrix for facility, job title, and calendar year. The total dust exposure data from China were converted to estimates of exposure to respirable crystalline silica for comparison with findings from other epidemiological studies of silicosis. Each worker's work history was abstracted from the complete employment records in mine files. Diagnoses of silicosis were based on 1986 Chinese pneumoconiosis Roentgen diagnostic criteria, which classified silicosis as stages I-III-similar to an International Labour Organisation (ILO) classification of 1/1 or greater. There were 10...