• Toxicological Research
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• v.17
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• pp.293-297
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• 2001

The international pharmaceutical and regulatory communities had been recognizing the limited utility of conventional rodent carcinogenicity study particularly on the second species, mouse, after intense investigation of carcinogenicity data base worldwide, and a new scheme for carcinogenicity testing for pharmaceuticals was proposed at the Expert Working Group on Safety in the International Conference on Harmonization (ICH) in 1996. CB6F 1-Tg rasH2 mouse carrying human prototype c-Ha-ras gene with its own promoter/enhancer is one oj the new carcinogenicity assay model for human cancer risk assessment. Studies have been conducted since 1992 to validate the transgenic (Tg) mice for rapid carcinogenicity test-ing, short term (26 weeks) studies with genotoxic (by Salmonella), non-genotoxic carcinogens, genotoxic non-carcinogens, non-genotoxic non-carcinogens revealed relatively high concordance oj the response of the Tg mouse with classical bioassay across classes of carcinogenic agents. Mechanistic basis for carcinogensis in the model are being elucidated in terms of the role of overexpression and/or point mutation of the transgene. This report review the initial studies of validation of the model and preliminary results of on-going ILSI HESI ACT project will be presented.

• Journal of Environmental Impact Assessment
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• v.29 no.5
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• pp.391-402
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• 2020

Health Impact Assessment based on municipal law is performed and written in the sanitary and public health part in the current environmental impact assessment. Residential development projects such as housing site development etc., are not subject to health impact assessment under Article 13 of the Environmental Health Act. However, health impact assessment is conducted partially based on the review that health impact assessment targets which are identified among substances emitted from pollutants nearby industrial complexes should be assessed risk (including carcinogenic and non-carcinogenic) at the stage of the environmental impact assessment consultation. Although residential development projects do not have plans for pollutant emitting facilities that emit hazardous air pollutants, there is a possibility that residents might be affected by pollutants from industrial complex near residential area in the future. In this study, Health impact assessment was conducted to examine the impact on residents in planned areas by analyzing previous residential development projects. We predicted future impact by using the literature survey results on surrounding area (case1) and conducting contribution analysis (case2) and predicting exposure concentration of carcinogenic substances applying Atmospheric Diffusion Model (AERMOD). By this study, we concluded that applying on-site survey, contribution analysis and prediction of exposure concentration by using AERMOD complementarily will be effective to assess the health impact to the receptors by pollutants from industrial complexes near the planned zone.

• Journal of Preventive Medicine and Public Health
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• v.31 no.2 s.61
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• pp.275-284
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• 1998

Activities of enzymes involved in the metabolism of various carcinogenic xenobiotics is one of the most important host factors for cancer occurrence. N-acetyltransferase (NAT) and glutathione S-transferases (GST) are enzymes which .educe the toxicity of activated carcinogenic metabolites. Slow N-acetylation and lack of GST mu (GSTMI) were reported as risk factors of bladder cancer. GST theta (GSTT1), which is another type of GST, was reported to be deleted at higher proportion among Koreans. Since cause of bladder cancer is not fully explained by single risk factor, many kinds of enzymes would be involved in the metabolism of carcinogens excreted in urine. This study was performed to investigate whether the polymorphisms of NAT2, GSTM1 and GSTT1 are risk factors of bladder cancer and to evaluate the effects of their interaction on bladder cancer development. Sixty-seven bladder cancer and 67 age- and sex-matched non-cancer patients hospitalized in Chungbuk National University Hospital from March to December 1996, are the subjects of this case-control study. Questionnaire interview was done and the genotypes of NAT2, GSTM1 and GSTT1 were identified using PCR methods with DNA extracted from venous blood. The effects of the polymorphism of NAT2 and GSTM1 and their interaction on bladder cancer were statistically tested after controlling the other risk factors. The frequencies of slow, intermediate, and rapid acetylators were 3.0%, 38.8%, and 58.2% to. the cases, and 7.6%, 40.9%, and 51.5% for the controls, respectively. The risk of bladder cancer was not associated with the increase of NAT2 activity($\chi^2_{trend}=1.18$, P-value>0.05). GSTM1 was deleted in 68.7% of the cases and 49.3% of the controls ($\chi^2=5.21$, P-value<0.05), and the odds ratio (95% CI) was 2.23 (1.12 - 4.56). GSTT1 deletion, the .ate of which were 26.9% for the bladder cancer patients and 43.3% for the controls, was a significant protective factor against bladder cancer. Smoking history turned out to be insignificant as a risk factor of bladder cancer (OR=1.85, 95% CI: 0.85 - 4.03), and occupation could not be tested because of the extremely small number of occupational history related to the increase of bladder cancer. In multiple logistic analysis controlling the effects of other risk factors, GSTM1 deletion was the only significant risk factor for bladder cancer (OR: 2.56, 95% CI: 1.22-5.36, P-value<0.05), but slow acetylation and GSTT1 deletion were not. These results suggest that GSTM1 deletion may be a significant risk factor of bladder cancer. Since there have been much debates on causal relationship between slow acetylation and GSTT1 deletion, and bladder cancer, further studies are needed.

• Asian Journal of Atmospheric Environment
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• v.8 no.1
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• pp.35-47
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• 2014

The purpose of the study is to evaluate the pollution level (gaseous and particle phase) in the public facilities for the PAHs, non-regulated materials, forecast the risk level by the health risk assessment (HRA) and propose the guideline level. PAH assessments through sampling of particulate matter of diameter < 2.5 ${\mu}m$ ($PM_{2.5}$). The user and worker exposure scenario for the PAHs consists of 24-hour exposure scenario (WIES) assuming the worst case and the normal exposure scenario (MIES) based on the survey. This study investigated 20 PAH substances selected out of 32 substances known to be carcinogenic or potentially carcinogenic. The risk assessment applies major toxic equivalency factor (TEF) proposed from existing studies and estaimates individual Excess Cancer Risk (ECR). The study assesses the fine dusts ($PM_{2.5}$) and the exposure levels of the gaseous and particle PAH materials for 6 spots in each 8 facility, e.g. underground subway stations, child-care facilities, elderly care facilities, super market, indoor parking lot, terminal waiting room, internet caf$\acute{e}$ (PC-rooms), movie theater. For internet caf$\acute{e}$ (PC-rooms) in particular, that marks the highest $PM_{2.5}$ concentration and the average concentration of 10 spots (2 spots for each cafe) is 73.3 ${\mu}g/m^3$ (range: 6.8-185.2 ${\mu}g/m^3$). The high level of $PM_{2.5}$ seen in internet cafes was likely due to indoor smoking in most cases. For the gaseous PAHs, the detection frequency for 4-5 rings shows high and the elements with 6 rings shows low frequency. For the particle PAHs, the detection frequency for 2-3 rings shows low and the elements with 6 rings show high frequency. As a result, it is investigated that the most important PAHs are the naphthalene, acenaphthene and phenanthrene from the study of Kim et al. (2013) and this annual study. The health risk assessment demonstrates that each facility shows the level of $10^{-6}-10^{-4}$. Considering standards and local source of pollution levels, it is judged that the management standard of the benzo (a)pyrene, one of the PAHs, shall be managed with the range of 0.5-1.2 $ng/m^3$. Smoking and ventilation were considered as the most important PAHs exposure associated with public facility $PM_{2.5}$. This study only estimated for inhalation health risk of PAHs and focused on the associated cancer risk, while multiple measurements would be necessary for public health and policy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5249-5252
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• 2014

Nogo protein, encoded by gene reticulon-4 (RTN4), includes three major isoforms by different splicing, named Nogo-A Nogo-B and Nogo-C. Nogo proteins play an important role in the apoptosis of cells, especially in tumor cells. RTN4 single nucleotide polymorphisms (SNPs) can influence the efficiency of transcription and translation thus being related with an individual's predisposition to cancer. The CAA insertion/deletion polymorphism (rs34917480) within RTN4 3'-UTR has been reported to be associated with many cancer types. In order to investigate the relationship between this polymorphism and susceptibility to non-small cell lung cancer (NSCLC) in the Chinese population, we conducted the present case-control study including 411 NSCLC patients and 471 unrelated healthy controls. The genotype distributions were significantly different between cases and controls (p=0.014). We found that the del allele could significantly increase NSCLC risk (ins/ins vs ins/del: p=0.007, OR 1.46, 95%CI=1.11-1.93; dominant model: p=0.004, OR 1.47, 95%CI=1.13-1.92 and allele model: p=0.008, OR 1.35, 95%CI=1.08-1.67). This association was stronger in participants over 60 years old, males and smokers. We therefore conclude that the CAA insertion/deletion polymorphism (rs34917480) contributes to non-small cell lung cancer risk in Chinese population. Age, sex and environmental exposure are also related to carcinogenic effects of rs34917480.

• Journal of Food Hygiene and Safety
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• v.35 no.4
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• pp.354-364
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• 2020

For this paper we analyzed heavy metals including lead, cadmium, arsenic and mercury, and conducted risk assessment on 171 types of herbal medicines used as foods and drugs distributed in Seoul's Yangnyeongsi and Kyungdong (Gyeongdong) herbal medicine markets. The concentrations of the heavy metals were measured by the ICP-MS and a mercury analyzer. The detection ranges of the lead, cadmium, arsenic and mercury were found to be ND-4.719 mg/kg, ND-1.019 mg/kg, 0.002-8.696 mg/kg and ND-0.058 mg/kg, respectively. Artemisiae Capillaris Herba exceeded the standards of the MFDS (Ministry of Food and Drug Safety) for cadmium items, and Actinidiae Ramulus et Fulium et Fructus Vermicultus exceeded the standards for arsenic items. The non-carcinogenic risk assessment showed that there were no items exceeding 1 and that they were safe. The risk of carcinogenicity to lead was below 10^-6 in all items and was evaluated as safe. The risk of carcinogenicity of arsenic was almost all in the range of 10^-4 to 10^-6. All %PTWI are considered to be safe below 100.

• Environmental Analysis Health and Toxicology
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• v.27
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• pp.12.1-12.8
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• 2012

Objectives: The aim of this study was to identify the health and environmental risk factors of air contaminants that influence environmental and respiratory diseases in Gyeongju, Pohang and Ulsan in South Korea, with a focus on volatile organic compounds (VOCs). Methods: Samples were collected by instantaneous negative pressure by opening the injection valve in the canister at a fixed height of 1 to 1.5 m. The sample that was condensed in $-150^{\circ}C$ was heated to $180^{\circ}C$ in sample pre-concentration trap using a 6-port switching valve and it was injected to a gas chromatography column. The injection quantity of samples was precisely controlled using an electronic flow controller equipped in the gas chromatography-mass spectrometer. Results: The quantity of the VOC emissions in the industrial area was 1.5 to 2 times higher than that in the non-industrial area. With regards to the aromatic hydrocarbons, toluene was detected at the highest level of 22.01 ppb in Ulsan, and chloroform was the halogenated hydrocarbons with the highest level of 10.19 ppb in Pohang. The emission of toluene was shown to be very important, as it accounted for more than 30% of the total aromatic hydrocarbon concentration. Conclusions: It was considered that benzene in terms of the cancer-causing grade standard, toluene in terms of the emission quantity, and chloroform and styrene in terms of their grades and emission quantities should be selected for priority measurement substances.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6429-6438
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• 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.

• BMB Reports
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• v.51 no.11
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• pp.584-589
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• 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.

• Journal of Food Hygiene and Safety
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• v.25 no.2
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• pp.148-152
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• 2010

Domestic studies for identification of causality between children exposure to toxic chemicals, such as arsenic (As) and resulted hazardous effects were not implemented. This study was conducted to probabilistically estimate dietary As intake and health risk assessment for young children and all age-specific populations from the consumption of As-contaminated rice of Korea. Arsenic intakes for young children (1 to 6 years old) from As-contaminated rice were higher than other age-specific groups, based on a dose-per-body weight basis. Based on the current EPA cancer slope factor for As, estimated cancer risks (to the skin cancer) associated with dietary intake of As-contaminated rice for 1 to 2 years old group and 3 to years old group are 1.76 per 10,000 and 3.16 per 10,000, respectively, at the 50th percentile. Based on possible reference levels (0.005 mg/kg/day) for children, mean and $95^{th}$ percentile value of HQ from rice for young children are very below 1.0, which is a regulatory limit of non-carcinogenic risks for human.