• Molecules and Cells
• /
• 제20권3호
• /
• pp.378-384
• /
• 2005

Estrogen metabolites are carcinogenic. The comparative mitogenic activities of $17{\beta}$-estradiol (E2) and four metabolites, 2-hydroxyestradiol (2-OHE2), 4-hydroxyestradiol (4-OHE2), $16{\alpha}$-hydroxyestrone ($16{\alpha}$-OHE1) and 2-methoxyestradiol (2-ME), were determined in estrogen receptor(ER)-positive MCF-7 human breast cancer cells. Each of the E2 metabolites caused proliferation of the MCF-7 cells, but only E2 and $16{\alpha}$-OHE1 induced a greater than 20-fold increases in transcripts of the progesterone receptor (PR) gene, a classical ER-mediated gene. This suggests that the mitogenic action of E2 and $16{\alpha}$-OHE1 could result from their effects on gene expression via the ER. E2 metabolites altered the expression of E2-regulated proteins including heat shock proteins (Hsps). $16{\alpha}$-OHE1 and 2-ME as well as E2 increased levels of Hsp56, Hsp60, $Hsp90{\alpha}$ and Hsp110 transcripts, and the patterns of these inductions resembled that of PR. Hsp56 and Hsp60 protein levels were increased by all the E2 metabolites. Levels of the transcripts of 3 E2-upregulated proteins (XTP3-transactivated protein A, protein disulfide isomerase-associated 4 protein and stathmin 1) and an E2-downregulated protein (aminoacylase 1) were also affected by the E2 metabolites. These results suggest that the altered expression of Hsps (especially Hsp56 and Hsp60) by E2 metabolites such as E2, $16{\alpha}$-OHE1 and 2-ME could be closely linked to their mitogenic action.

• Environmental Sciences Bulletin of The Korean Environmental Sciences Society
• /
• 제10권S_3호
• /
• pp.113-119
• /
• 2001

Surface sediments(0~5 cm) were sampled from 22 stations in Ulsan Bay, one of the most highly industrialized regions in Korea, in November 2000. The sediment samples were analyzed for their polycyclic aromatic hydrocarbon(PAH) content using a gas chromatography coupled to a mass spectrometer detector(GC/MSD). The total PAH concentrations in the sediments varied from 14 to 7108 ng/g dry weight with a mean value of 1052 ng/g dry weight. The level of carcinogenic PAHs ranged from 6 to 2396 ng/g dry weight with a mean value of 433 ng/g dry weight. The highest PAH concentrations in the sediments from Ulsan Bay were found at Station U8, whereas the lowest levels were observed at Stations U2 and U 17. The PAH distribution exhibited a decreasing gradient from the inner basin to the outer bay. The predominant contributors to the aromatic ring groups of the 16 PAHs were four- and five-ring groups, such as fluoranthene, pyrene, benzo[a]anthracene, chrysene, benzor[b]fluoranthene, benzor[k]fluoranthene and benzo[a]pyrene, while two- and three-ring aromatics, like naphthalene, acenapthylene, acenaphthene, fluorene, phenanthrene and anthracene, only exhibited a low concentration. The molecular indices for phenanthrene/anthracene and fluoranthen/pyrene were used to Identify the origin of the PAH contamination in the sediments. The results indicated that the PAH contamination in Ulsan Bay was mostly Pyrolytic in origin with a Petrogenic input adjacent to Ulsan and Jangsuengpo harbor.

• Journal of Microbiology
• /
• 제43권4호
• /
• pp.319-324
• /
• 2005

Estuarine sediments are frequently polluted with hydrocarbons from fuel spills and industrial wastes. Polycyclic aromatic hydrocarbons (PAHs) are components of these contaminants that tend to accumulate in the sediment due to their low aqueous solubility, low volatility, and high affinity for particulate matter. The toxic, recalcitrant, mutagenic, and carcinogenic nature of these compounds may require aggressive treatment to remediate polluted sites effectively. In petroleum-contaminated sediments near a petrochemical industry in Gwangyang Bay, Korea, in situ PAH concentrations ranged from 10 to 2,900 ${\mu}g/kg$ dry sediment. To enhance the biodegradation rate of PAHs under anaerobic conditions, sediment samples were amended with biostimulating agents alone or in combination: nitrogen and phosphorus in the form of slow-release fertilizer (SRF), lactate, yeast extract (YE), and Tween 80. When added to the sediment individually, all tested agents enhanced the degradation of PAHs, including naphthalene, acenaphthene, anthracene, fluorene, phenanthrene, fluoranthene, pyrene, chrysene, and benzo [a] pyrene. Moreover, the combination of SRF, Tween 80, and lactate increased the PAH degradation rate 1.2-8.2 times above that of untreated sediment (0.01-10 ${\mu}g$ PAH/ kg dry sediment/day). Our results indicated that in situ contaminant PAHs in anoxic sediment, including high molecular weight PAHs, were degraded biologically and that the addition of stimulators increased the biodegradation potential of the intrinsic microbial populations. Our results will contribute to the development of new strategies for in situ treatment of PAH-contaminated anoxic sediments.

• BMB Reports
• /
• 제52권11호
• /
• pp.647-652
• /
• 2019

G protein-coupled estrogen receptor (GPER) is known to play an important role in hormone-associated cancers. G-1, a novel synthetic GPER agonist, has been reported to exhibit anti-carcinogenic properties. However, the chemotherapeutic mechanism of GPER is yet unclear. Here, we evaluated GPER expression in human gastric cancer tissues and cells. We found that G-1 treatment attenuates GPER expression in gastric cancer. GPER expression increased G-1-induced antitumor effects in mouse xenograft model. We analyzed the effects of knockdown/overexpression of GPER on G-1-induced cell death in cancer cells. Increased GPER expression in human gastric cancer cells increased G-1-induced cell death via increased levels of cleaved caspase-3, -9, and cleaved poly ADP-ribose polymerase. Interestingly, during G-1-induced cell death, GPER mRNA and protein expression was attenuated and associated with ER stress-induced expression of PERK, ATF-4, GRP-78, and CHOP. Furthermore, PERK-dependent induction of ER stress activation increased G-1-induced cell death, whereas PERK silencing decreased cell death and increased drug sensitivity. Taken together, the data suggest that the induction of ER stress via GPER expression may increase G-1-induced cell death in gastric cancer cells. These results may contribute to a new paradigm shift in gastric cancer therapy.

• 한국환경성돌연변이발암원학회지
• /
• 제23권2호
• /
• pp.56-62
• /
• 2003

The liver progenitor cells could form a potential target cell population fore both tumor-initiating and -promoting chemicals. Induction of drug-metabolizing and antioxidant enzymes, including AhR-dependent CYP1A1, NQO-1 and AKR1C9, was detected in the rat liver epithelial WB-F344 "stem-like" cells. Additionally, WB-F344 cells express a functional, wild-type form of p53 protein, a biomarker of genotoxic events, and connexin 43, a basic structural unit of gap junctions forming an important type of intercellular communication. In this cellular model, two complementary assays have been established for detection of the modes of action associated with tumor promotion: inhibition of gap junctional intercellular communication (GJIC) and proliferative activity in confluent cells. We found that the PAHs and PCBs, which are AhR agonists, released WB-F344 cells from contact inhibition, increasing both DNA synthesis and cell numbers. Genotoxic effects of some PAHs that lead to apoptosis and cell cycle delay might interfere with the proliferative activity of PAHs. Contrary to that, the nongenotoxic low-molecular-weight PAHs and non-dioxin-like PCB congeners, abundant in the environment, did not significantly affect cell cycle and cell proliferation; however both groups of compounds inhibited GJIC in WB-F344 cells. The release from contact inhibiton by a mechanism that possibly involves the AhR activation, inhibition of GJIC and genotoxic events induced by environmental contaminants are three important modes of action that could play an important role in carcinogenic effects of toxic compounds. The relative potencies to inhibit GJIC, to induce AhR-mediated activity, and to release cells from contact inhibition were determined for a large series of PAHs and PCBs and their metabolites. In vitro bioassays based on detection of events on cellular level (deregulation of GJIC and/or proliferation) or determination of receptor-mediated activities in both ?$stem-like^{\circ}{\times}$ and hepatocyte-like liver cellular models are valuable tools for detection of modes of action of polyaromatic hydrocarbons. They may serve, together with concentration data, as a first step in their risk assessment.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권4호
• /
• pp.2461-2476
• /
• 2013

To assess environmental contamination with carcinogens, carbonaceous compounds, water-soluble ionic species and trace gaseous species were identified and quantified every three hours for three days st three different atmospheric layer at the heart of chiang-Mai, bangkok and hat-Yai from December 2006 to February 2007. A DRI model 2001 Themal/Optical Carbon Analyzer with the IMPROVE thermal/optical reflectance (TOR) protocol was used to quantify the organic carbon(OC) and elemental carbon content in $PM_{10}$. Diurnal and vertical variability was also carefully investigated. In general, OC and EC contenttration shoeed the highest values at the monitoring period o 21.00-00.00 as consequences of human activities at night bazaar coupled with reduction of mixing layer, decreased wind speed and termination of photolysis nighttime. Morning peaks of carboaceous compounds were observed during the sampling period of 06:00 -09:00, emphasizing the main contribution of traffic emission in the three cities. The estimation of incremental lifetime partculate matter exposure (ILPE) raises concern of high risk of carbonaceous accumulation over workers and residents living close to the observatory sites. The average values of incremental lifrtime particulate matter exposure (ILPE) of total carbon at Baiyoke Suit Hotel and Baiyoke Sky Hotel are approsimately ten time shigher then those air sample collected at prince of songkla University Hat-Yai campus corpse incinerator and fish-can maufacturing factory but only slightly higher than those of rice straw burnig in Songkla province. This indicates a high risk of developing lung cancer and other respiratory diseases across workers and residents living in high buildings located in Pratunam area. Using knowledge of carbonaceous fractions in $PM_{10}$, one can estimate the gas-particle partitioning of polycyclic aromatic hydrocarbons (PAHs). Dachs-Eisenreich model highlights the crucial role of adsorption in gas-particle partitioning of low molecular weight PAHs, whereas both absorption and adsorption tend to account for gas-particle partitioning of high molecular weight PAHs in urban residential zones of Thailand. Interestingly, the absorption mode alone plays a minor role in gas-partcle partitiining of PAHs in Chiang-Mai, Bangkok and hat-Yai.

• BMB Reports
• /
• 제51권11호
• /
• pp.584-589
• /
• 2018

Secondary prevention via earlier detection would afford the greatest chance for a cure in premalignant lesions. We investigated the exomic profiles of non-malignant and malignant changes in head and neck squamous cell carcinoma (HNSCC) and the genomic blueprint of human papillomavirus (HPV)-driven carcinogenesis in oropharyngeal squamous cell carcinoma (OPSCC). Whole-exome (WES) and whole-genome (WGS) sequencing were performed on peripheral blood and adjacent non-tumor and tumor specimens obtained from eight Korean HNSCC patients from 2013 to 2015. Next-generation sequencing yielded an average coverage of $94.3{\times}$ for WES and $35.3{\times}$ for WGS. In comparative genomic analysis of non-tumor and tumor tissue pairs, we were unable to identify common cancer-associated early mutations and copy number alterations (CNA) except in one pair. Interestingly, in this case, we observed that non-tumor tonsillar crypts adjacent to HPV-positive OPSCC appeared normal under a microscope; however, this tissue also showed weak p16 expression. WGS revealed the infection and integration of high-risk type HPV16 in this tissue as well as in the matched tumor. Furthermore, WES identified shared and tumor-specific genomic alterations for this pair. Clonal analysis enabled us to infer the process by which this transitional crypt epithelium (TrCE) evolved into a tumor; this evolution was accompanied by the subsequent accumulation of genomic alterations, including an ERBB3 mutation and large-scale CNAs, such as 3q27-qter amplification and 9p deletion. We suggest that HPV16-driven OPSCC carcinogenesis is a stepwise evolutionary process that is consistent with a multistep carcinogenesis model. Our results highlight the carcinogenic changes driven by HPV16 infection and provide a basis for the secondary prevention of OPSCC.

• 한국환경과학회지
• /
• 제15권5호
• /
• pp.405-415
• /
• 2006

Sixteen soil samples around six areas (residental area, traffic area, power plant area, incineration area and factory area) where the stationary and mobile sources of polycyclic aromatic hydrocarbons (PAHs) are estimated to be emitted in Jeju City, were collected during Feburuary to March, 2004, and analyzed for 16 PAHs recommended by US EPA as primary pollutants to investigate their distribution characteristics. The concentrations of total PAHs (t-PAHs) and total carcinogenic PAHs $(t-PAH_{CARC})$ in soils of Jeju City were in the range of $21.7\sim264.2ng/g$ on a dry weight basis with a mean value of 87.2 ng/g and $6.3\sim118.0ng/g$ with a mean value of 33.4 ng/g, respectively. The concentrations of t-PAHs were low in comparison with those in soils of other domestic and foreign countries. The mean concentrations of t-PAHs and $(t-PAH_{CARC})$ with area decreased in the following sequences: traffic area> incineration area > factory area > power generation area > harbor area enli residental area. The correlation between t-PAHs and $(t-PAH_{CARC})$ were very high $(\gamma^2=0.9701)$, indicating that $(t-PAH_{CARC})$ concentration increases in proportion with t-PAHs. Comparing the distribution ratio of ring PAHs with area among 16 PAHs, it decreased in the order of 4-ring > 5-ring > 6-ring > 3-ring > 2-ring in all the areas except for harbor area. whitens for harbor area it was similar among 3-, 4- and 5-ring with high value. Low and no correlations between t-PAHs and soil compositions (organic matter content and particle size distribution) were observed, which is considered to be caused by the complex factors, such as the loading and characteristics of PAHs and diverse soil environment change, etc. From the examination of the three PAH origin indices, such as LMW/HMW (low molecular weight $2\sim3$ ring PAHs over high molecular weight $4\sim6$ ring PAHs), phenanthrene/anthracene ratio and fluoranthene/pyrene ratio, it can be concluded that the soil PAH contaminations were ascribed to strong pyrogenic origin in ail areas except for harbor area and to both pyrogenic and petrogenic origins.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권15호
• /
• pp.6429-6438
• /
• 2015

Glutathione S-transferases (GSTs) play an important role in detoxification of carcinogenic electrophiles. The null genotypes in GSTM1 and GSTT1 have been implicated in carcinogenesis. Present study was planned to evaluate the influence of genetic polymorphisms of GSTM1 and GSTT1 gene loci in cervical carcinogenesis. The study was conducted in Lok Nayak hospital, New Delhi. DNA from clinical scrapes of 482 women with minor gynaecologic complaints attending Gynaecology OPD and tumor biopsies of 135 cervical cancer cases attending the cancer clinic was extracted. HPV DNA was detected by standard polymerase chain reaction (PCR) using L1 consensus primer pair. Polymorphisms of GSTM1 and GSTT1 were analysed by multiplex PCR procedures. Differences in proportions were tested using Pearson's Chi-square test with Odds ratio (OR) and 95% confidence interval (CI). The risk of cervical cancer was almost three times in women with GSTM1 homozygous null genotype (OR-2.62, 95%CI, 1.77-3.88; p<0.0001). No association of GSTM1 or GSTT1 homozygous null genotypes was observed in women with normal, precancerous and cervical cancerous lesions among ${\leq}35$ or >35 years of age groups. Smokers with null GSTT1 genotype had a higher risk of cervical cancer as compared to non-smokers (OR-3.01, 95% CI, 1.10-8.23; p=0.03). The results further showed that a significant increased risk of cervical cancer was observed in HPV positive smoker women with GSTT1 (OR-4.36, 95% CI, 1.27-15.03; p=0.02) and GSTM1T1 (OR-3.87, 95% CI, 1.05-14.23; p=0.04) homozygous null genotypes as compared to HPV positive non smokers. The results demonstrate that the GST null genotypes were alone not associated with the development of cervical cancer, but interacted with smoking and HPV to exert effects in our Delhi population.

• 한국대기환경학회지
• /
• 제22권5호
• /
• pp.574-589
• /
• 2006

Although concentrations of hazardous air pollutants(HAPs) are very low in the atmosphere, a growing attention has been paid on such compounds due to their high toxicity and bioaccumulation potentials into human body. In order to control and manage the amount of these materials in ambient air, it is necessary to construct monitoring system of them and to know the current concentration level of HAPs above all. In this work, a wide range of HAPs has been measured in metropolitan area to recognize the present state of HAPs in this area. The measured concentration of VOCs was higher in order of Jeonnongdong, Jeongdong, and Yangsuri. The regional difference of VOCs concentration was also highest in spring. Its total VOCs was ranged from $15.17{\sim}41.45$ ppb. Benzene $0.43{\sim}2.32$ ppb showed similar concentration level with the result of previous researches in Seoul. This value is a little higher than the average concentration 0.92 ppb for national ambient air quality standards in Japan. The concentration of aldehydes in this study was lower than those of other researches. Previous works in Seoul metropolitan area showed that the concentration of formaldehyde and acetaldehyde were higher than 5 ppb. The concentration of gaseous and particulate PAHs was high in order of winter, spring, and summer More than 90% of PAHs with low molecular weight such as 2-rings and 3-rings PAHs existed in gas phase. On the other hands, PAHs with high molecular weight more than 5-rings PAHs almost existed in particulate. In spring, the concentration of gaseous PAHs was 24.38 $ng/m^3$ in Jeongdong. Among the particulate PAHs, the concentrations of Naphthalene, Benzo(b)fluoranthene, and Benzo(g, h, i)perylene were higher than others. Especially, the concentration of Benzo(a)pyrene, a important carcinogenic pollutant, was highest in winter 0.5 $ng/m^3$ and ranged from 0.03 to 0.3 $ng/m^3$ in spring and summer, which is lower than the monitoring result in 90's. These components were mainly originated from the vehicle exhaust or heating equipment use.