Effects of Styrene-metabolizing Enzyme Polymorphisms and Lifestyle Behaviors on Blood Styrene and Urinary Metabolite Levels in Workers Chronically Exposed to Styrene

Kim, Ki-Woong Korean Society of ToxicologyKorea Environmental Mu 2015 Toxicological Research Vol.31 No.4

The aim of this study was to investigate whether genetic polymorphisms of CYP2E1, GSTM1, and GSTT1 and lifestyle habits (smoking, drinking, and exercise) modulate the levels of urinary styrene metabolites such as mandelic acid (MA) and phenylglyoxylic acid (PGA) after occupational exposure to styrene. We recruited 79 male workers who had received chronic exposure in styrene fiberglass-reinforced plastic manufacturing factories. We found that serum albumin was significantly correlated with blood styrene/ambient styrene (BS/AS), urinary styrene (US)/AS, and US/BS ratios as well as urinary metabolites, that total protein correlated with US/MA and US/PGA ratios, and that low density lipoprotein (LDL)-cholesterol significantly correlated with US/BS, US/MA, and US/PGA ratios. Multiple logistic regression analyses using styrene-metabolizing enzyme genotypes and lifestyle habits as dependent variables and blood and urine styrene concentrations and urine styrene metabolite levels as independent variables revealed that $CYP2E1^*5$ was associated with the MA/US ratio and GSTM1 with US/BS, that a smoking habit was associated with US/AS and MA/US ratios and MA and PGA levels, and that regular exercise was correlated with PGA/US. In conclusion, the results suggested that genetic polymorphisms of styrene-metabolizing enzymes, lifestyle behaviors, and albumin and LDL-cholesterol serving as homeostasis factors together are involved in styrene metabolism.

Effects of Styrene-metabolizing Enzyme Polymorphisms and Lifestyle Behaviors on Blood Styrene and Urinary Metabolite Levels in Workers Chronically Exposed to Styrene

김기웅 한국독성학회 2015 Toxicological Research Vol.31 No.4

The aim of this study was to investigate whether genetic polymorphisms of CYP2E1, GSTM1, and GSTT1 and lifestyle habits (smoking, drinking, and exercise) modulate the levels of urinary styrene metabolites such as mandelic acid (MA) and phenylglyoxylic acid (PGA) after occupational exposure to styrene. We recruited 79 male workers who had received chronic exposure in styrene fiberglass-reinforced plastic manufacturing factories. We found that serum albumin was significantly correlated with blood styrene/ambient styrene (BS/AS), urinary styrene (US)/AS, and US/BS ratios as well as urinary metabolites, that total protein correlated with US/MA and US/PGA ratios, and that low density lipoprotein (LDL)-cholesterol significantly correlated with US/BS, US/MA, and US/PGA ratios. Multiple logistic regression analyses using styrene-metabolizing enzyme genotypes and lifestyle habits as dependent variables and blood and urine styrene concentrations and urine styrene metabolite levels as independent variables revealed that CYP2E1*5 was associated with the MA/US ratio and GSTM1 with US/BS, that a smoking habit was associated with US/AS and MA/US ratios and MA and PGA levels, and that regular exercise was correlated with PGA/US. In conclusion, the results suggested that genetic polymorphisms of styrene-metabolizing enzymes, lifestyle behaviors, and albumin and LDL-cholesterol serving as homeostasis factors together are involved in styrene metabolism.

Styrene 및 Styrene-oxide가 송사리 알의 초기발생 과정에 미치는 독성 : Oryzias latipes

박형숙,안혜원 한국환경독성학회 2000 환경독성보건학회지 Vol.15 No.3

Toxic lesions of styrene in the Japanese Medaka (Oryzias latipes) were compared with those of styrene oxide, the active metabolite of styrene, using embryo-larval assays. The developmental stages of Japanese Medaka (Oryzias latipes) treated with both chemicals were not altered and progressed normally. However, styrene oxide was more toxic than styrene in terms of causing death and lesions. High concentrations of styrene (higher than 4.9 ppm) and styrene oxide (higher than 2.4 ppm), resulting in more than 50% mortality, caused similar lesions of cardiovascular system, craniofacial bone formation and spinal deformities, although a number of lesions were not observed by both chemicals. In the group treated with styrene, eyeball sizes and intereye distances were reduced, while, in the group treated with styrene oxide, the eyes and eye cups were not developed and two eyes were sometimes fused. In addition, styrene oxide caused the lesion which involved the posterior brain and brain stem were herniated through the spinal cord. The noticeable difference of toxic symptoms between these two chemicals was the time of onset. Toxicities of cardiovascular system and craniofacial bone formation appeared on day 3 of development in styrene oxide treated group, but, styrene treated group stared to show hemorrhages on day 3 and the craniofacial malformation were appeared on day 5. These differences between two chemicals may be due to the metabolism of styrene to styrene oxide, the reactive intermediate.

Styrene Cytotoxicity in Testicular Leydig Cells In Vitro

정진영,박지은,김윤재,김종민,유욱준,이승진 한국발생생물학회 2022 발생과 생식 Vol.26 No.3

Styrene is the precursor of polystyrene. Human exposure to styrene could occur in occupational and residential settings and via food intake. Styrene is metabolized to styrene- 7,8-oxide by cytochrome P450 enzyme. In the present study, we investigated the cytotoxicity mediated by styrene and styrene-7,8-oxide in TM3 testicular Leydig cells in vitro. We first monitored the nuclear fragmentation in Leydig cells after exposure to styrene or styrene-7,8- oxide. Hoechst 33258 cell staining showed that styrene exposure in TM3 Leydig cells did not exhibit nuclear fragmentation at any concentration. In contrast, nuclear fragmentation was seen in styrene-7,8-oxide-exposed cells. These results indicate that cytotoxicity-mediated cell death in Leydig cells is more susceptible to styrene-7,8-oxide than to styrene. Following styrene treatment, procaspase-3 and XIAP protein levels did not show significant changes, and cleaved (active) forms of caspase-3 were not detected. Consistent with the western blot results, the active forms of caspase-3 and XIAP proteins were not prominently altered in the cytoplasm of cells treated with styrene. In contrast to styrene, styrene-7,8-oxide induced cell death in an apoptotic fashion, as seen in caspase-3 activation and increased the expression of XIAP proteins. Taken together, the results obtained in this study demonstrate a fundamental idea that Leydig cells are capable of protecting themselves from cytotoxicitymediated apoptosis as a result of styrene exposure in vitro. It remains unclear whether the steroid-producing function, i.e., steroidogenesis, of Leydig cells is also unaffected by exposure to styrene. Therefore, further studies are needed to elucidate the endocrine disrupting potential of styrene in Leydig cells.

Effects of Styrene-metabolizing Enzyme Polymorphisms and Lifestyle Behaviors on Blood Styrene and Urinary Metabolite Levels in Workers Chronically Exposed to Styrene

Ki-Woong Kim 한국독성학회 2015 Toxicological Research Vol.31 No.4

The aim of this study was to investigate whether genetic polymorphisms of CYP2E1, GSTM1, and GSTT1 and lifestyle habits (smoking, drinking, and exercise) modulate the levels of urinary styrene metabolites such as mandelic acid (MA) and phenylglyoxylic acid (PGA) after occupational exposure to styrene. We recruited 79 male workers who had received chronic exposure in styrene fiberglass-reinforced plastic manufacturing factories. We found that serum albumin was significantly correlated with blood styrene/ambient styrene (BS/AS), urinary styrene (US)/AS, and US/BS ratios as well as urinary metabolites, that total protein correlated with US/MA and US/PGA ratios, and that low density lipoprotein (LDL)-cholesterol significantly correlated with US/BS, US/MA, and US/PGA ratios. Multiple logistic regression analyses using styrene-metabolizing enzyme genotypes and lifestyle habits as dependent variables and blood and urine styrene concentrations and urine styrene metabolite levels as independent variables revealed that CYP2E1<SUP>*</SUP>5 was associated with the MA/US ratio and GSTM1 with US/BS, that a smoking habit was associated with US/AS and MA/US ratios and MA and PGA levels, and that regular exercise was correlated with PGA/US. In conclusion, the results suggested that genetic polymorphisms of styrene-metabolizing enzymes, lifestyle behaviors, and albumin and LDL-cholesterol serving as homeostasis factors together are involved in styrene metabolism.

Styrene 노출에 반응을 보이는 혈청 단백질에 대한 프로테오믹스 분석

김기웅 ( Ki Woong Kim ),허경화 ( Kyung Hwa Heo ),원용림 ( Yong Lim Won ),정진욱 ( Jin Wook Jeong ),김태균 ( Tae Gyun Kim ),박인정 ( In Jeong Park ) 한국산업위생학회 2007 한국산업보건학회지 Vol.17 No.3

By comparing the proteins from the workers exposed to styrene with the ones from controls, it may be possible to identify proteins that play a role in the occurrence and progress of occupational disease and thus to study the molecular mechanisms of occupational disease. In order to find the biomarkers for assessing the styrene effects early, before clinical symptoms develop and to understand the mechanisms of adverse health effects, we surveyed 134 employees, among whom 52 workers(30 male and 22 female) were chronically exposed to styrene in 10 glass-reinforced plastic boat manufacturing factories in Korea and 82 controls had never been occupationally exposed to hazardous chemicals including styrene. The age and drinking habits and serum biochemistry such as total protein, BUN and serum creatinine in both groups were significantly different. Exposed workers were divided into three groups according to exposure levels of styrene(G1, below 1/2 TLV; G2, 1/2 TLV to TLV; G3, above TLV). The mean concentration of airborne styrene in G1 group was 10.93±11.33 ppm, and those of urinary mandelic acid(MA) and phenylglyoxylic acid(PGA) were 0.17±0.21 and 0.13±0.11 g/g creatinine, respectively. The mean concentration of airborne styrene in G2 and G3 groups were 47.54±22.43 and 65.33±33.47 ppm, respectively, and levels of urinary metabolites such as MA and PGA increased considerably as expected with the increase in exposure level of styrene. The airborne styrene concentration were significantly correlated to the urinary concentration of MA(r=0.784, p=0.000) and PGA(r=0.626, p<0.001). In the 2D electrophoresis, the concentration of five proteins including complement C3 precursor, alpha-1-antitrypsin(AAT), vitamin D binding protein precursor(DBP), alpha-1-B-glycoprotein(A1BG) and inter alpha trypsin inhibitor(ITI) heavy chain-related protein were significantly altered in workers exposed to styrene compared with controls. While expression of complement C3 precursor and AAT increased by exposure to styrene, expression of DBP, A1BG and ITI heavy chain-related protein decreased. These results suggest that the exposure of styrene might affects levels of plasma proteinase, carriers of endogenous substances and immune system. In particular, increasing of AAT with the increase in exposure level of styrene can explain the tissue damage and inflammation by the imbalance of proteinase/antiproteinase and decrease of DBP, A1BG and ITI heavy chain-related protein in workers exposed to styrene is associated with dysfunction and/or declination in immune system and signal transduction.

스티렌 폭로 근로자들의 기중 및 혈중 스티렌과 요중 만델산의 관계 분석

정호근,강성규,양정선,김기웅,이종성,조영숙,박인정 大韓産業醫學會 1994 대한직업환경의학회지 Vol.6 No.1

The concentration of styrene in air in blood and mandelic acid in urine were checked for the 60 workers with normal liver function, exposed to styrene. Styrene in air were sampled with personal air sampler at least 4 hours and analyzed by gas chromatography. Blood and spot urine were collected at the end of shift with a vacuum tube and a polythylene bottle and analyzed by gas chromatography and high performance liquid chromatography. Means of air and blood styrene and urine mandelic acid were 8.16 ppm(geometric mean), 0.199 mg/L, and 0.519 g/g creatinine, respectively. The concentration of styrene in air and mandelic acid in urine were high in the FRP factories and low in polymerization factory. Styrene in blood showed large difference by the working process. Styrene in air showed a good correlation with mandelic acid in urine(r=0.6369) and styrene in blood(r=0.6371). The mandelic acid in urine and styrene in blood corresponded to exposure of 50 ppm styrene were 0.890 g/g creatinine and 0.434 mg/L. However, hippuric acid in urine did not show any correlation with styrene in air. Urine mandelic acid excretion expected ratio showed a tendency to decrease according to obesity index and to increase with alcohol consumption.

스타이렌과 산화스타이렌에 의한 소핵 유도

이세영,이세훈 가톨릭대학산업의학센타 산업의학연구소 1999 韓國의 産業醫學 Vol.38 No.1

Styrene is a commercially important chemical used mainly in the production of polymers and reinforced plastics. Human erythrocytes, lymphocytes can oxidize styrene to styrene-7,8-oxide in the absence of the co-factors required for metabolic reactions catalyzed by the microsomal cytochrome P-450 system. Styrene has been reported to produce chromosomal aberrations, micronuclei and sister chromatid exchanges in human whole-blood lymphocyte cultures. This study was designed to investigate whether styrene or styrene-7,8-oxide induce micronuclei(MN) in phytohaemagglutinin-stimulated human whole-blood lymphocytes culture. Fresh heparinized peripheral blood samples from a healthy donor (male, smoker) was cultured in the phytohaemagglutinin stimulated RPMI media. Styrene and styrene-7,8-oxide were injected into the cultures. Cytochalasin-B was added into the cultures for cytokinesis-block. Micronuclei were analyzed in 1000 binucleated lymphocytes from each duplicated cultures on coded acridine orange stained slides. The results were as follows: 1. Average frequency of micronuclei in binucleated lymphocytes treated with styrene was not significantly increased at any concentration applied in this study. But, styrene-7,8-oxide showed a significant induction of micronuclei in 0.125, 0.500mM concentration. 2. Styrene and styrene-7,8-oxide significantly decresed replication index(RI). The results of this study demonstrated that styrene-7,8-oxide could contribrte to the genotoxicity of styrene in human whole-blood lymphocyte.

흰쥐에 있어서 Styrene에 의한 간장의 Microsomal Cytochrome P450의 유도

이준연,박상신,정효석,문영한,김기웅,장성근 大韓産業醫學會 1997 대한직업환경의학회지 Vol.9 No.4

The effects of styrene on the induction of cytochrome P-450s (P450), (P4501A1/2, P4502B1/2 and P4502E1) and activities of other related enzymes were investigated in the male Sprague Dawley rats which were treated with styrene 500(S1), 1.000(S2), 1,500(S3) mg/kg in olive oil intraperitoneally once a day for two days and sacrificed for the preparation of liver microsomes after 24 hrs. 1. The contents of total protein and P450 in the microsomes derived from the styrene treated groups were slightly higher than those from the control group except those from the S3 group (1,500 mg styrene/kg body weight). The decreases in microsomal protein contents was prominent in the S3 (p<0.05), but the P450 contents was increased significantly in the S2(P<0.05). 2. The activities of NADPH-450 and NADH b5 reductase in hepatic microsomes derived from the treated groups were significantly increased in the treated groups (p<0.05). 3. The activities of PROD were also prominently increased with the treatment of styrene except in S3 group, but the activity of EROD was decreased by styrene treatment. The activities of pNPH in the styrene treated groups were higher than that of the control group(p<0.05). 4. Western blotting with monoclonal antibodies against P4502B1/2 isozymes showed the presence of P4502B1/2 in hepatic microsomes from the rats treated with styrene, and the increase in the densities of immunoblots were corelated with the dosages of styrene. The blot densities against P4501A1/2 and P4502E1 were slightly increased in the styrene treated groups compared with the control group. These results suggested that styrene could primarily induce P4502B1/2 as major and P4501A1/2 and P4502E1 in minor forms for the metabolism of styrene in rats.

Analytical method for determination of microstructures of solution styrene-butadiene copolymers using 2-phenylpropene/styrene ratio of pyrolysis products

Choi, Sung-Seen,Kwon, Hyuk-Min Elsevier 2015 POLYMER TESTING -LONDON- Vol.44 No.-

<P><B>Abstract</B></P> <P>Raw and cured solution styrene-butadiene rubbers (S-SBRs) with different microstructures were pyrolyzed and the pyrolysis products were analyzed using gas chromatography/mass spectrometry. 2-Phenylpropene (2-PP) was newly found to be formed from butadiene-styrene heterosequence. Formations of 2-PP and styrene were competitive and their relative intensities varied depending on the microstructure. Intensity ratios of 2-PP/styrene were plotted as a function of the 1,2-unit, 1,4-unit and styrene contents in order to employ the 2-PP/styrene plots as calibration curves to determine microstructure of unknown S-SBR samples. The 2-PP/styrene plot as a function of the 1,2-unit content had better correlation coefficients than those of the styrene and 1,4-unit contents. Correlation coefficients of the 2-PP/styrene plots were improved by correction with the 1,2-unit mole fraction. Microstructures (1,2-unit, 1,4-unit, and styrene contents) of unknown S-SBR samples could be determined using the 2-PP/styrene calibration curves.</P>