<i>In vivo</i> genotoxicity evaluation of lung cells from Fischer 344 rats following 28 days of inhalation exposure to MWCNTs, plus 28 days and 90 days post-exposure

Kim, Jin Sik,Sung, Jae Hyuck,Choi, Byung Gil,Ryu, Hyeon Yeol,Song, Kyung Seuk,Shin, Jae Hoon,Lee, Jong Seong,Hwang, Joo Hwan,Lee, Ji Hyun,Lee, Gun Ho,Jeon, Kisoo,Ahn, Kang Ho,Yu, Il Je Informa Healthcare 2014 INHALATION TOXICOLOGY Vol. No.

<P>Despite their useful physico-chemical properties, carbon nanotubes (CNTs) continue to cause concern over occupational and human health due to their structural similarity to asbestos. Thus, to evaluate the toxic and genotoxic effect of multi-wall carbon nanotubes (MWCNTs) on lung cells <I>in vivo</I>, eight-week-old rats were divided into four groups (each group = 25 animals), a fresh air control (0 mg/m<SUP>3</SUP>), low (0.17 mg/m<SUP>3</SUP>), middle (0.49 mg/m<SUP>3</SUP>), and high (0.96 mg/m<SUP>3</SUP>) dose group, and exposed to MWCNTs <I>via</I> nose-only inhalation 6 h per day, 5 days per week for 28 days. The count median length and geometric standard deviation for the MWCNTs determined by TEM were 330.18 and 1.72 nm, respectively, and the MWCNT diameters ranged from 10 to 15 nm. Lung cells were isolated from five male and five female rats in each group on day 0, day 28 (only from males) and day 90 following the 28-day exposure. The total number of animals used was 15 male and 10 female rats for each concentration group. To determine the genotoxicity of the MWCNTs, a single cell gel electrophoresis assay (Comet assay) was conducted on the rat lung cells. As a result of the exposure, the olive tail moments were found to be significantly higher (<I>p</I> < 0.05) in the male and female rats from all the exposed groups when compared with the fresh air control. In addition, the high-dose exposed male and middle and high-dose exposed female rats retained DNA damage, even 90 days post-exposure (<I>p</I> < 0.05). To investigate the mode of genotoxicity, the intracellular reactive oxygen species (ROS) levels and inflammatory cytokine levels (TNF-α, TGF- β, IL-1, IL-2, IL-4, IL-5, IL-10, IL-12 and IFN-γ) were also measured. For the male rats, the H<SUB>2</SUB>O<SUB>2</SUB> levels were significantly higher in the middle (0 days post-exposure) and high- (0 days and 28 days post-exposure) dose groups (<I>p</I> < 0.05). Conversely, the female rats showed no changes in the H<SUB>2</SUB>O<SUB>2</SUB> levels. The inflammatory cytokine levels in the bronchoalveolar lavage (BAL) fluid did not show any statistically significant difference. Interestingly, the short-length MWCNTs deposited in the lung cells were persistent at 90 days post-exposure. Thus, exposing lung cells to MWCNTs with a short tube length may induce genotoxicity.</P>

일부 인쇄회로기판 납땜근로자들의 눈, 호흡기, 피부의 증상에 대한 조사연구

유재영,우극현,김진석,함정오,최태성,하봉구,정상재,박신구,김일룡 大韓産業醫學會 2001 대한직업환경의학회지 Vol.13 No.4

목적 : 이 연구는 납점작업자를 대상으로 납점작업으로 유발될 가능성이 높은 눈, 호흡기, 피부 등의 증상호소율 및 노출강도에 따른 관련성을 파악하기위해 수행되었다. 방법 : 연구참가자 146명중 연구목적에 적합한 20명을 제외한 126명을 대상으로 '눈이 가렵고 충혈됨', '코가 가렵거나 파가움', '재채기', '콧물'. '코막힘' , '목이 따끔거림' , '목에 무언가가 걸려있는것 같음' , '갑자기 연속적인 기침을 함' , '운동 시에 다른 사람에 비해 숨이 가쁨', '숨을 쉴 때 쌕쌕하는 소리가 남', '가래가 끓음', '손이나 안면에 가려움을 느낌' , '안면에 여드름이 날' '손이나 안면에 붉은 반점이 남' 등 14가지 증상에 대한 경험유무와 혈중연농도, 납점작업의 건강위험요인에 대한 지식상태 등을 조사하였다. 결과 : 조사된 14가지의 증상 중, '갑자기 연속적인 기침을 함'이 하루 납점시간 4시간 이상인 군아서 4시간 미만인 군보다 유의하게 증상호소율이 높았으며, 다른 증상의 경우 하루 납땜시간에 따라 유의한 결과를 보이지 않았다. 납땜작업의 건강위험요인에 대한 질문에 12.8 %가 플럭스에 의한 건강위험을 지적하였다. 전체 대상자의 평균 혈중연농도는6.05 rg/dL였으며, 히고치는 15.50 rg/dL이었다.결론 : 납땜작업자에게 호흡기 증상의 위험이 높을 가능성이 있으며, 납땜작업의 건강위험에 대한추가적인 연구와 납점작업자들을 대상으로 납점작업에 의해 유발될 수 있는 건강장해에 대한 적극적인교육 및 홍보활동을 필요로 한다. Objectives : This study was conducted to evaluate the prevalence of ocular, respiratory and skin symptoms among solderers and to investigate the relationship between symptom prevalence and exposure intensity. Methods : We analyzed 126 eligible participants out of a population of 146 male solder-ers who completed the symptom questionnaires. Fourteen symptoms including 'itchy and red eyes', 'itchy or prickly nose', 'sneezing', 'rhinorrhea', 'blocked nose', 'prickly throat', 'foreign body sensation in throat', 'sudden bouts of coughing', 'exertional breathlessness', 'wheezing', 'sputum production', 'itchy face or hands', 'acneiform erup-tions on the face' and 'red spots on the face or hands' were contained. Blood lead levels of all the 126 participants were tested and the participants' own assessments of the health risk of soldering were collected. Results : Of the 14 investigated symptoms, 'sudden bouts of coughing' was significantly more prevalent in solderers who worked 4 hours or more a day than those who worked less than 4 hours a day, as for the other symptoms, there were no significant differences in the prevalences related to daily soldering hours. 2.8% of the solderers considered the risk of flux exposure to be serious. The mean blood lead bevel was 6.05 μg/dL (maximum 15.50 μg/dL). Conclusions : Soldering may increase the risk of respiratory symptoms. Further invert tigations on the hazards of soldering processes are warranted and solderers should be educarted on these hazards.

Mycophenolic Acid와 Rapamycin이 흰쥐 사구체 혈관간세포증식과 세포외기질 생성에 미치는 영향

김명수,박제현,하헌주,허규하,서지연,김유선,김혜진,박기일 이화여자대학교 약학연구소 2004 藥學硏究論文集 Vol.- No.14

Background: Excess proliferation and extracellular matrix (ECM) accumulation of mesenchymal cells such as vascular smooth muscle cells (VSMC) and glomerular mesangial cells cause chronic allograft nephropathy showing transplant vascular sclerosis and glomerulosclerosis. Mycophenolic acid (MPA) and rapamycin (RPM) are well known as strong inhibitors of VSMC proliferation, but their effects on the glomerular mesangial cells are not yet clearly understood. This study examined the effects of MPA or RPM on PDGF-induced proliferation and ECM accumulation in rat glomerular mesangial cells. Methods: Mesangial cells isolated from the glomeruli of Sprague-Dawley rats were cultured with DMEM containing 20% fetal bovine serum. Growth arrested and synchronized cells were administered with test drugs (MPA10 nM-10μM, RPM 0.1 nM-1μM) before the addition of PDGF 10 ng/mL. Cell proliferation was assessed by [³H]thymidine incorporation, collagen by [³H]proline incorporation, and fibronectin, ERK, and p38 MAPK by Western blot analysis. Results: PDGF increased mesangial cell proliferation by 4.64-fold. Compared to stimulated control, MPA above 500 nM and RPM above 10nM showed a significant inhibitory effect in a dose-dependent manner. The IC_(50) of MPA and RPM against PDGF-induced mesangial cell proliferation were around 500 nM and 100 nM, respectively. The collagen synthesis was also inhibited by MPA and RPM, but the fibronectin secretion was inhibited by MPA alone. The proliferation of mesangial cell correlated with activation of ERK and. p38 MAPK. MPA, but not RPM, inhibited ERK and p38 MAPK activation. Conclusion: This study demonstrated that MPA and RPM significantly inhibited PDGF-induced proliferation and ECM production in rat glomerular mesangial cells. The inhibitory effects of MPA, but not RPM, are correlated with ERK and p38 MAPK.

남성화 암쥐의 모리스 수중 미로 수행력 : 성에 따른 공간기억력과 테스토르테론 효과의 차이

신성현,박제민,정우영,박문일,서유나,김성곤,강철중 大韓神經精神醫學會 2007 신경정신의학 Vol.46 No.5

Objectives : It is widely accepted that gonadal steroids are involved in organization and activation of sexual dimorphism in the brain areas related with spatial leaming. This study aimed to test the following hypothesis : 1) spatial memory is affected by sex, 2) this difference is related with brain differentiation by exposure to testosterone in the neonatal period, and/or 3) the sexual difference of spatial memory is the result of the interaction between organization of sexual dimorphism in the brain and the circulating testosterone after growing up. Methods : Testosterone enanthate 100 ㎍, ('androgenized') orvehicle ('control') was randomly administered to 28 female and 25 male rat pups within 24 hour of birth. The escape latencies (EL) in Morris water maze were measured in 15 and 16 week of age with vehicle ('baseline') and with 10 μmol/kg of testosterone ('with testosterone'), respectively. Each session Consis-ted of 10 trials, and means of the last 5 trials were analyzed. Results : The baseline EL of the males were significantly shorter than females regardless ofneonatal exposure to testosterone. With testosterone, EL of the androgenized females were significantly shorter than control females and comparable to those of males. Conclusion : Neonatal exposure to testosterone in female rats may develop a tesosterone-dependent male-like spatial leaming system.

Threshold Rigidity Values for the Asbestos-like Pathogenicity of High-Aspect-Ratio Carbon Nanotubes in a Mouse Pleural Inflammation Model

Lee, Dong-Keun,Jeon, Soyeon,Han, Youngju,Kim, Sung-Hyun,Lee, Seonghan,Yu, Il Je,Song, Kyung Seuk,Kang, Aeyeon,Yun, Wan Soo,Kang, Sung-Min,Huh, Yun Suk,Cho, Wan-Seob American Chemical Society 2018 ACS NANO Vol.12 No.11

<P>The qualitative and quantitative evaluation of the physicochemical parameters associated with the pathogenicity of high-aspect-ratio nanomaterials is important for comprehensive regulation efforts and safety-by-design approaches. Here, we report quantitative data on the correlations between the rigidity of these nanomaterials and toxicity endpoints <I>in vitro</I> and <I>in vivo</I>. As measured by new ISO standards published in 2017, rigidity shows a strong positive correlation with inflammogenic potential, as indicated by inflammatory cell counts and IL-1β (a biomarker for frustrated phagocytosis) levels in both the acute and chronic phases. <I>In vitro</I> experiments using differentiated THP-1 cells find that only highly rigid multiwalled carbon nanotubes (MWCNTs) and asbestos fibers lead to piercing and frustrated phagocytosis. Thus, this study suggests a bending ratio of 0.97 and a static bending persistence length of 1.08 as threshold rigidity values for asbestos-like pathogenicity. However, additional research using MWCNTs with rigidity values that lie between those of non-inflammogenic (<I>D</I><SUB>b</SUB> = 0.66 and SBPL = 0.87) and inflammogenic fibers (<I>D</I><SUB>b</SUB> = 0.97 and SBPL = 1.09) is required to identify more accurate threshold values, which would be useful for comprehensive regulation and safety-by-design approaches based on MWCNTs.</P> [FIG OMISSION]</BR>

방진마스크의 Stainless steel arc 용접흄 여과효율에 관한 연구

송경석,권용식,한규태,정규혁,이용묵,유일재 한국산업위생학회 2001 한국산업보건학회지 Vol.11 No.1

The purpose of this study was to investigate for filtration efficiency of several dust masks, comparing with filtration efficiency certified by KOSHA(Korea Occupational Safety & Health Agency), and to require of the right use of protective respirator. Using a welding fume generator and chamber, several dust masks, which were widely used in the workplaces in korea, were tested for their filtering efficiency for stainless steel are welding fume. The filtration efficiency testing system consisted of a welding fume generator, a chamber and a filtration unit. The filtration unit was made of a mask which was inserted into the sampling cassette and another sampling cassette, which contained mixed cellulose ester filter paper. These two cassettes were connected with tubing. Stainless steel arc welding fume generator was delivered into an chamber. The welding fume in the chamber was passed into the filtration unit with flow rate of 30 liter/min. The welding fume filtration efficiency was evaluated by gravimetric measurement. Metal concentrations in the welding fume before and after filtration were measured with inductive coupling plasma analyzer. Following results were obtained: Filtration efficiency of welding fume for comm hygienic mas was 63.82% and the average efficiencies for A, B, C, D, E, F and G masks were 94.62% 96.58%, 83.20%, 82.76%, 77.25%, 86.55% and 93.22%, respectively. Our results indicate that dust masks used widely in the welding workplaces in korea are not proper for protecting worker's health and then the use of fume mask should be required.

3-MCPD의 생식˙발생독성에 관한 연구

곽승준(Seung Jun Kwack),김순선(Soon Sun Kim),최요우(Yo Woo Choi),이규식(Gyu Seek Rhee),손경희(Kyung Hee Sohn),이이다(Rhee Da Lee),채수영(Soo Young Chae),정용현(Yong-Hyun Chung1),유일재(Il Je Yu1),박귀례(Kui Lea Park) 한국독성학회 2004 Toxicological Research Vol.20 No.2

3-Monochloro-1,2-propanediol(3-MCPD) is a toxic compound, often present in different foods containing acid hydrolyzed(AH) protein, like seasonings and savory food products. The purpose of the present study was to investigate the effects of 3-MCPD on male fertility, sperm and testosterone secretion. In vivo male fertility test was performed for observing the adverse effects of 3-MCPD on the function of male reproductive system and pregnancy outcome. 0.01, 0.05, 0.25, 1 and 5 mg/kg b.w. of 3-MCPD was given daily by gavage to groups of 15 adult male SD rats for 4 weeks. At the end of pre-treatment period, males were mated overnight with normal females. Following morning, males demonstrating successful induction of pregnancy were sacrificed on that day to assess sperm parameters and histopathology of reproductive organs. The resulting pregnant females were sacrificed on day 20 of gestation to evaluate pregnancy outcome. As a result, four-week paternal administration with 3-MCPD resulted in adverse effects on male fertility and pregnancy outcome without remarkable histopathological changes in testes and epididymides; sperm motility, copulation index and fertility index were markedly decreased in the treated group and numbers of live fetuses showed steep dose-response curves. Also, spermatogenesis was investigated in this experiment. However, no<br/> effect was observed on production of sperm in testes treated with 3-MCPD for 4 weeks. Hormone assay was performed for observing the effects of 3-MCPD on testosterone and luteinizing hormone (LH) in blood and testes of male SD rats and cultured primary Leydig cell. In result, significant changes of related hormones did not observed by treatment of 3-MCPD. These results indicated that paternal treatment with 3-MCPD induced spermatotoxic effect, which caused an antifertility on male.

Occupational and Environmental Health Effects of Nanomaterials

Yu, Il Je,Gulumian, Mary,Shin, Sehyun,Yoon, Tae Hyun,Murashov, Vladimir Hindawi Publishing Corporation 2015 BioMed research international Vol.2015 No.-

Effect of benzo(a)pyrene and mitomycine C on HeLa cell division cycle

Yu, Il-Je,Lim, Cheol-Hong,Kim, Hyo-Jung,Chung, Kyu-Hyuk,Song, Kyung-Seuk,Han, Jeong-Hee,Chung, Yong-Hyun Korean Environmental Mutagen Society 2001 한국환경성돌연변이·발암원학회지 Vol.21 No.2

Recently, there has been significant progress in understanding the control process of the cell division cycle. To investigate the influence of toxic substances on the cell cycle, the effect of benzo(a)pyrene (BAP) and mitomycine C (MMC) on synchronized HeLa cells was analyzed during the cell cycle. To synchronize the HeLa cells, 10$^{6}$ cells were grown for 1 day and then treated with 1 mM hydroxyurea for 14 h. The arrested cells were then allowed to proceed through their cell cycle by removing the hydroxyurea and resupplying a fresh medium. The arrested cells in the G1/S transition then proceeded to the S phase after 4 h, the G2/M phase after 8h, and the G1 phase after 12 h, subsequent to the resupply of a fresh medium. In the untreated HeLa cells, the p34$^{cdc2}$ kinase activity, measured using a p34$^{cdc2}$ specific peptide, peaked after 8h (G2/M) and then declined after 12 h (G1). However, treatment with 30 $\mu$M BAP delayed the peak of the p34$^{cdc2}$ kinase activity. The amount of p34$^{cdc2}$ remained unchanged in the untreated, BAP-, and MMC-treated cells throughout the cell cycle. The cyclin B level peaked after 8 h in the untreated cells, yet peaked after 10-12 h in the BAP-treated cells. There was no significant change in the cyclin B level in the MMC-treated cells.

Effect of benzo(a)pyrene and mitomycine C on HeLa cell division cycle

Il Je Yu,Cheol Hong Lim,Hyo Jung Kim,Kyu Hyuk Chung,Kyung Seuk Song,Jeong Hee Han,Yong Hyun Chung 한국환경성돌연변이발암원학회 2001 한국환경성돌연변이·발암원학회지 Vol.21 No.2

Recently, there has been significant progress in understanding the control process of the cell division cycle. To investigate the influence of toxic substances on the cell cycle, the effect of benzo(a)pyrene (BAP) and mitomycine C (MMC) on synchronized HeLa cells was analyzed during the cell cycle. To synchronize the HeLa cells, 106 cells were grown for 1 day and then treated with 1 mM hydroxyurea for 14 h. The arrested cells were then allowed to proceed through their cell cycle by removing the hydroxyurea and resupplying a fresh medium. The arrested cells in the G1/S transition then proceeded to the S phase after 4 h, the G2/M phase after 8h, and the G1 phase after 12 h, subsequent to the resupply of a fresh medium. In the untreated HeLa cells, the p34cdc2 kinase activity, measured using a p34cdc2 specific peptide, peaked after 8h (G2/M) and then declined after 12 h (G1). However, treatment with 30 μM BAP delayed the peak of the p34cdc2 kinase activity. The amount of p34cdc2 remained unchanged in the untreated, BAP-, and MMC-treated cells throughout the cell cycle. The cyclin B level peaked after 8 h in the untreated cells, yet peaked after 10-12 h in the BAP-treated cells. There was no significant change in the cyclin B level in the MMC-treated cells.