• Biomedical Science Letters
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• v.24 no.3
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• pp.143-149
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• 2018

Excessive exposure to estrogens is the most important risk factor for the development of hormone-sensitive cancers, especially breast cancer. Estrogen stimulates the expression of genes and proteins involved in cell proliferation by binding to estrogen receptor (ER). Another possible mechanism of ER-independent carcinogenicity of estrogens is based on the hydroxylation of estradiol resulting in the formation of catechol estrogens. Catechol estrogen 4-hydroxyestradiol ($4-OHE_2$) is further oxidized to catechol estrogen-3,4-quinones, the major carcinogenic metabolites of estrogens. Evidence increasingly supports the critical role of $4-OHE_2$ in hormonal carcinogenesis via DNA adduct formation or production of reactive oxygen species, which finally contribute to the transformation of normal mammary epithelial cells and the enhanced growth of breast cancer cells. It is also reported that the level of $4-OHE_2$ or its quinones is highly up-regulated in urine or tissues of breast cancer patients. Thus, we highlight the oncogenic roles of $4-OHE_2$ in catechol estrogen-induced breast carcinogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2625-2628
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• 2012

Introduction: Fumonisin B1 (FB1) is a toxic and carcinogenic mycotoxin produced in cereals due to fungal infection. This study was conducted to determine FB1 contamination of rice and corn samples and its relationship with the rate of esophageal cancer (EC) in a high risk area in northeastern Iran. Methods: In total, 66 rice and 66 corn samples were collected from 22 geographical subdivisions of Golestan province of Iran. The levels of FB1 were measured for each subdivision by thin layer and high pressure liquid chromatographies. The mean level of FB1 and the proportions of FB1 contaminated samples were compared between low and high EC-risk areas of the province. Results: The mean of FB1 levels in corn and rice samples were 223.64 and 21.59 ${\mu}g/g$, respectively. FB1 contamination was found in 50% and 40.9% of corn and rice samples, respectively. FB1 level was significantly higher in rice samples obtained from high EC-risk area (43.8 ${\mu}g/g$) than those obtained from low risk area (8.93 ${\mu}g/g$) (p-value=0.01). The proportion of FB1 contaminated rice samples was also significantly greater in high (75%) than low (21.4%) EC-risk areas (p-value=0.02). Conclusion: We found high levels of FB1 contamination in corn and rice samples from Golestan province of Iran, with a significant positive relationship between FB1 contamination in rice and the risk of EC. Therefore, fumonisin contamination in commonly used staple foods, especially rice, may be considered as a potential risk factor for EC in this high risk region.

• 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.

• Analytical Science and Technology
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• v.35 no.3
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• pp.93-115
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• 2022

Potential impurities in pharmaceuticals could be produced during manufacture, distribution, and storage and affect quality and safety of pharmaceuticals. In particular, highly reactive impurities could result in carcinogenic (mutagenic) effects on human body. International Conference on Harmonisation (ICH) has provided M7(R1) guideline for "Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk" and recommended an adoption of this guideline to the authorities. ICH M7(R1) guideline provides classification, accepted intakes, and controls of potential impurities in pharmaceuticals. However, since appropriate and unified analytical methods for impurities in pharmaceuticals have not been provided in this guideline, most potential impurities in pharmaceuticals are still difficult to manage and supervise by pharmaceutical companies and regulatory authorities, respectively. In this review, we briefly described definition of unintended mutagenic impurities, basic information in ICH M7(R1) guideline, and analytical methods to determine potential impurities. This review would be helpful to manage and supervise potential impurities in pharmaceuticals by pharmaceutical companies and regulatory authorities.

• Journal of Environmental Health Sciences
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• v.45 no.6
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• pp.646-657
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• 2019

Objectives: The purpose of this study was to suggest methods to investigate continuous monitoring of concentration levels and assess the exposure of individuals considering the actual time activity of residents for formaldehyde and particulate matter (PM₁₀, PM_2.5) in the indoor and outdoor air of a house, assess the health risks of children and adults based on the results of the exposure assessment, and provide basic data on studies for assessing exposure and health risks in Korea in the future. Methods: The concentration levels of formaldehyde and particulate matter were measured in a family home in Gyeonggi-do Province from April 25 to July 31, 2019, using electrochemical sensors (formaldehyde) and light scattering sensors (PM₁₀, PM_2.5). Risk assessment by the duration of exposure by time activity was performed by dividing between weekdays and weekends, and indoors and outdoors. Results: The greatest level of carcinogenic risk from inhaling formaldehyde was indoors during the weekdays for both children and adults. For children, the risk was at 7.5 per approximately 10,000 people, and for adults, the risk was at 4.1 per approximately 10,000 people. PM₁₀ and PM_2.5 also showed the greatest values indoors during the weekdays, with children at 1.7 people and 1.4 per approximately 100 people, respectively, and adults at 8.2 per approximately 1,000 and 1.8 per approximately 100 people, respectively. Conclusions: The risks of formaldehyde, PM₁₀ and PM_2.5 were shown to be high indoors. Therefore, consideration of exposure assesment for each indoor pollutant and management of indoor air quality is necessary.

• Journal of Environmental Health Sciences
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• v.33 no.4
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• pp.242-249
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• 2007

Indoor air quality has become a topic of interest and concern. Especially changes in construction design and the increased use of synthetic products may result in an increasing of complaints and health effects about the quality of indoor air at home. In this study, nitrogen dioxide($NO_2$) and volatile organic compounds(VOCs) within new and established apartments on the basis of 4 years of building year were measured every 3 days consecutively during 60 days. We selected each 10 house in Seoul, Asan and Daegu, respectively, and produced risk numbers for hazard quotients, and predicted increases in incidence of cancer. The calculations were made for the adult with default exposure values and also made for a worst case scenario using Monte-Carlo simulation as describing the reasonable exposure(RME). Mean of Monte carlo analysis by benzene, in the construction under 4 years (male: $9.2{\times}10^{-5}$, female: $1.0{\times}10^{-4}$) and over 4 years (male: $6.8{\times}10^{-5}$, female: $8.3{\times}10^{-5}$) exceeded $10^{-6}$ of permitted standards in US EPA, RME of Monte carlo analysis. In construction under 4 yews (male: $9.9{\times}10^{-3}$, female: $9.6{\times}10^{-3}$) and over 4 years (male: $9.8{\times}10^{-3}$, female: $7.8{\times}10^{-3}$) exceeded $10^{-4}$ of maximum permitted standards in US EPA. The hazard index of non-carcinogenic pollutants by nitrogen dioxide, toluene, m,p-xylene and o-xylene, both male and female in apartment constructed under 4 yews and over 4 years was found less than the permitted standards of hazardous health effects in CTE. Significant cancer risks and non-cancer hazard quotients were predicted in under 4 yews of building year.

• Environmental Engineering Research
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• v.11 no.5
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• pp.277-284
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• 2006

The genetic toxicity of environmental pollutants, namely, nonylphenol (NP), bisphenol A (BPA) and chloropyriphos (CP) was investigated in aquatic sentinel species, freshwater crustacean, Daphnia magna, and larva of aquatic midge, Chironomus tentans, using Comet assay. Physiological effect of such pollutants was also investigated by studying the specimens' rates of reproduction, growth and survival. Acute toxicity results showed that, as expected, Daphnia was more sensitive than Chironomus to chemical exposure. The order of acute toxicity was CP > NP > BPA in D. magna and NP > CP > BPA in C. tentans. BPA may exert a genotoxic effect on D. magna and C. tentans, given that DNA strand breaks increased in both species exposed to this compound, whereas NP- and CP-induced DNA damage occurred only in C. tentans. In vivo genotoxic data obtained in aquatic sentinel species could provide valuable information for freshwater quality monitoring. The experiments with NP-exposed D. magna showed that the pollutant has long-term effects on reproduction, whereas no short-term effect on DNA integrity was found, being an example of a false-negative result from the biomarkers perspective. This result could be interpreted that other mechanism than genetic alteration might be involved in NP-induced reproduction failure in D. magna. False-positive results from the genotoxic biomarker obtained in BPA-exposed D. magna and in NP-exposed C. tentans make it difficult to use DNA integrity as an early warning biomarker. However, as the mere presence of genotoxic compounds, which are potentially carcinogenic, is of high concern to human and ecosystem health, it could also be important to rapidly and effectively detect genotoxic compounds in the aquatic system in ways that do not necessarily accompany a higher level of alteration. Considering the potential of D. magna and C. tentans as bioindicator species, and the importance of genotoxic biomarkers in ecotoxicity monitoring, DNA damage in these species could provide useful information for environmental risk assessment.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10457-10462
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• 2015

Homologous recombination repair (HRR) plays an important role in protection against carcinogenic factors. Genes regulating the HRR mechanisms may impair their functions and consequently result in increased cancer susceptibility. RAD 51 and XRCC3 are key regulators of the HRR pathway and genetic variability in these may contribute to the appearance and progression of various cancers including head and neck cancer (HNC). The aim of the present study was to compare the distribution of genotypes of RAD51 (135G/C, 172 G/T) and XRCC3 (Thr241Met) polymorphisms between HNC patients and controls. Each polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymerase (PCR-RFLP) technique in 200 pathologically confirmed HNC patients along with 150 blood samples from normal, disease free healthy individuals. We observed that homozygous variant CC genotype of RAD51 135G/C was associated with a 2.5 fold increased HNC risk (OR=2.5; 95%CI=0.69-9.53; p<0.02), while second polymorphism of RAD 51 172 G/T, heterozygous variant GT genotype was associated with a 1.68 fold (OR=1.68; 95%CI=1.08-2.61; p<0.02) elevation when compared with controls. In the case of the Thr241Met polymorphism of XRCC3, we observed a 16 fold (OR=16; 95% CI=3.78-69.67; p<0.0002) increased HNC risk in patients compared to controls. These results further suggested that RAD51 (135G/C, 172 G/T) and XRCC3 (Thr241Met) polymorphisms may be effective biomarkers for genetic susceptibility to HNC. Larger studies are needed to confirm our findings and identify the underlying mechanisms.

• Journal of Environmental Health Sciences
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• v.38 no.4
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• pp.277-290
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• 2012

Objectives: Diesel engine exhaust (DE) accounts for a significant percentage of air pollutants that are associated with various health outcomes including mortality, asthma, chronic bronchitis, respiratory tract infection, etc. In June, 2012, the International Agency for Research on Cancer (IARC) released the assessment results that classified DE as "carcinogenic to humans" (Group 1). This review is therefore focused on the lung cancer risks of DE. Methods: Literatures were searched using PubMed with key words of "diesel exhaust", "lung cancer", and other related terms for the period between 1990 and 2012. A total of 295 articles were searched and sixteen epidemiologic studies were identified as potentially relevant. Results: Sixteen epidemiologic studies about the lung cancer risks of workers exposed to DE in various occupations were summarized in two tables, 1) retrospective cohort studies and 2) case-control studies. Increased lung cancer risk, although not always smoking adjusted, was observed in 6 out of 8 retrospective cohort studies and 4 of 8 case-control studies. Conclusions: Diesel fuel is widely used in Korea. Exposure to DE is confirmed to be a human carcinogen by IARC. Noncancer health risks of DE also need careful attention as DE is a major source of fine-particle pollution. Along with the efforts for reducing the DE emission through improvements of diesel engines and fuel, and the use of alternative fuels, comprehensive health risk assessment of DE should be conducted to minimize the adverse health effects.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3047-3052
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• 2012

The enzyme encoded by the MGMT gene is involved in the repair of alkylated lesions formed in DNA by carcinogenic nitrosamines. Since dietary items consumed by the Kashmiri population contain high concentrations of these agents, it is biologically plausible that MGMT polymorphic variants may be associated with their risk of esophageal cancer. The present study was performed to assess whether non-synonymous SNPS at codon Leu84Phe and codon Ileu143Val of the MGMT gene, close to the active site of the protein, might be linked to predisposition of Kashmiris to esophageal cancer. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism on 92 cases and 77 healthy controls. Codon 84 and codon 143 SNPs of the MGMT gene were not associated with any increase in risk. While the frequency of the Phe allele at codon 84 in cases was (0.16), slightly higher than controls (0.12), the difference was not statistically significant. Similarly, the frequency of Valine allele in cases at codon 143 (0.08) and controls (0.09) was nearly equal. Moreover, no significant association of MGMT genotypes with the clinicopatholgic variables of esophageal cancer patients was observed. In conclusion, MGMT variants at codon 84 and codon143 may not be involved in the susceptibility of the Kashmiri population to esophageal cancer.