• Journal of Environmental Health Sciences
• /
• v.37 no.6
• /
• pp.429-439
• /
• 2011

Objectives: Ethylene oxide (EtO) is classified as a human carcinogen, but EtO is still widely used to sterilize heat-sensitive materials in hospitals. Employees working around sterilizers are exposed to EtO after sterilization. The aim of the present study was to assess the exposure of EtO level, coupled with occupationally induced micronuclei from hospital workers. The influence of genetic polymorphisms of detoxifying genes (GSTT1 and GSTM1) and DNA repair genes (XRCC1 and XRCC3) on the frequencies of micronuclei in relation to exposure of EtO was also investigated. Methods: The study population was composed of 35 occupationally exposed workers to EtO, 18 student controls and 44 unexposed hospital controls in Korea. Exposure to EtO is measured by passive personal samplers. We analyzed the frequencies of micronuclei by performing cytokinesis-block micronucleus assay (CBMN assay) and GSTM1, GSTT1, XRCC1, and XRCC3 were also genotyped by performing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The frequencies of micronuclei in EtO exposure group, student controls and hospital controls were $18.00{\pm}7.73$, $10.47{\pm}7.96$ and $13.86{\pm}6.35$ respectively and their differences were statistically significant, but no significant differences according to the level of EtO were observed. There was a dose-response relationship between the frequencies of micronuclei and cumulative dose of EtO, but no significantly differences were observed. We also investigated the influence of genetic polymorphisms (GSTM1, GSTT1, XRCC1, and XRCC3) on the frequencies of micronuclei, but there were no differences in the frequencies of micronuclei by genetic polymorphisms. Conclusions: The frequencies of micronuclei in EtO exposure group was significantly higher than control groups. A dose-response relationship was found between the level of EtO exposure and the frequencies of micronuclei, but no statistically differences were observed. We also found that the frequencies of micronuclei were increased according to cumulative EtO level. There was no association of the genetic GSTM1, GSTT1, XRCC1, and XRCC3 state with the frequency of micronuclei induced by EtO exposure.

• Tuberculosis and Respiratory Diseases
• /
• v.47 no.5
• /
• pp.650-659
• /
• 1999

Background/Aims: It is well recognized that all aerobic cells have the protective mechanisms in order to minimize the tissue damage induced by various reactive oxygen species(ROS). Thioredoxin peroxidase(TPX) which has been recently identified and characterized functions to convert peroxide to water. The protein is also found in various subtypes(TPX-A & B, MER5, HS22 and HORF-06) and is known to be ubiquitous in most human cells. Especially, ischemic brain injuries, partial hepatectomy and radiation induced DNA damages. In treating lung cancer, radiation therapy has a major place in the local control and the relief of symptoms, but radiation induced free radical injury and resulting pulmonary fibrosis has been the major drawback of the therapy. However, little is known about the protective mechanisms and biologic modulations against radiation-induced tissue damages. Methods: Eighteen mice were divided into six groups, 3 in each group, and fifteen had received 900cGy of radiation. The mice were sacrificed according to the pre determined time schedule; immediate, 1, 2, 3 and 6 weeks after irradiation. Extracts were made from the lungs of each mice, Western blot analysis of various subtypes of TPX were done after SDS-P AGE. Examination of H & E stained slides from the same irradiated specimens and the control specimens were also performed. Results: No difference in the intensity of the immunoreactive bands in the irradiated lung samples of the mice compared to the unirradiated control was observed regardless of the time intervals, although H & E examination of the sample specimens demonstrated progressive fibrotic changes of the irradiated lung samples. Conclusion: In conclusion, according to our data, it is suggested that various thioredoxin peroxidase subtypes and catalase which are known to be increased in many repair processes may not be involved in the repair of the radiation injury to the lung and subsequent fibrosis.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• v.22 no.4
• /
• pp.373-382
• /
• 2000

Individual genetic susceptibilities to cancers may result from several factors including differences in xenobiotics metabolism to chemical carcinogens, DNA repair, altered oncogenes and suppressor genes, and environmental carcinogen exposures. Among them, genetic polymorphisms of metabolizing enzymes to chemical carcinogens have been recognized as a major important host factors in human cancers. They have two main types of enzymes: the phase I cytochrome P-450 mediating enzymes (CYPs) and phase II conjugating enzymes. The purpose of this study is to determine the frequencies of genotypes of phase I (CYP1A1 and CYP2E1) and phase II (NAT2) metabolizing enzymes in healthy control and head and neck cancer patients of Korean and to identify the relative high risk genotypes of these metabolizing enzymes to head and neck cancer in Korean. The author has analyzed 132 head and neck cancer patients and 113 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results were as following; 1. The frequencies of genotypes of CYP1A1, CYP2E1 and NAT2 in healthy control were as following; CYP1A1 exon 7 polymorphism; Ile/Ile: Ile/Val: Val/Val = 59.3%: 36.3%: 4.4% CYP2E1 Pst I polymorphism, C1/C1: C1/C2: C2/C2 = 61.1%: 32.1%: 6.2% NAT2 polymorphism; F/F: F/S: S/S = 43.4%: 48.7%: 8.0% 2. In analysis of phase I enzyme, Val/Val genotype in CYP1A1 exon 7 polymorphism and C2/C2 genotype in CYP2E1 Pst I polymorphism were associated with relative high risks to head and neck cancers (Odds' ratio: 2.09 and 1.37, respectively). 3. Among the genotypes of NAT2 enzyme polymorphism, S/S genotype of NAT2 enzyme had 1.03 times of relative risk to head and neck cancers. 4. In combined genotyping of CYP1A1, CYP2E1, and NAT2 enzymes polymorphisms, the patients with Val/Val and C1/C1, C2/C2 and fast acetylator, and Val/Val and fast acetylator had higher relative risks than the patients with each baseline of combined genotypes (Odds' ratio: 2.82, 1.98 and 2.1, respectively). These results suggest the combined genotypes of Val/Val and C1/C1, C2/C2 and fast acetylator, and Val/Val and fast acetylator were more susceptible to head and neck cancers in Korean. And genotyping of metabolizing enzymes could be useful for predicting individual susceptibility to head and neck cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.2
• /
• pp.683-687
• /
• 2012

Ku70 plays an important role in DNA double-strand break repair. Studies revealing conflicting results on the role of the Ku70-1310C/G promoter polymorphism on cancer risk led us to perform a meta-analysis to investigate this relationship. Ten case-control studies with 2566 cases and 3058 controls were identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of associations. The overall results suggested no association between the Ku70-1310C/G promoter polymorphism and total cancer risk. However, on stratified analysis, significantly increased risks were observed among the Asian population (GG vs. CC: OR=1.50, 95%CI=1.10-2.06; GG vs. CC/CG: OR=1.47, 95%CI=1.07-2.01) and population-based case-control studies (GG vs. CC: OR=1.57, 95%CI=1.12-2.22; CG vs. CC: OR=1.35, 95%CI=1.11-1.64; CG/GG vs. CC: OR=1.37, 95%CI=1.14-1.65). Additionally, variant genotypes were associated with a significantly increased breast cancer risk (GG vs. CC: OR=1.80, 95%CI=1.26-2.56; GG vs. CC/CG: OR=1.40, 95%CI=1.01-1.95).

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.9
• /
• pp.4783-4788
• /
• 2012

Objective: Previous studies of the association between X-ray cross-complementing group 1 (XRCC1) gene polymorphisms and the gliomas risk have yielded conflicting results, and thus a meta-analysis was performed to provide a more accurate estimation. Methods: A computerized literature search of 5 electronic databases was conducted to identify the relevant studies. Fixed or random effect models were selected based on the heterogeneity test. Publication bias was estimated using Begg's funnel plots and Egger's regression test. Results: A total of 11 studies (3,810 cases and 6,079 controls), 7 studies (2,928 cases and 5,048 controls), and 4 studies (1,461 cases and 2,593 controls) were finally included in the analyses of the association between XRCC1 Arg399Gln, Arg194Trp, and Arg280His polymorphisms and glioma risk, respectively. The pooled results showed that GlnGln carriage was associated with moderately increased risk of gliomas in Asians (GlnGln vs. ArgArg, OR=1.490, 95%CI 1.031-2.153; GlnGln/ArgGln vs. ArgArg, OR=1.321, 95%CI 1.037-1.684), whereas a marginal association was revealed in Caucasians. For the Arg194Trp polymorphism, although a significant association was shown in the homozygous genotype comparisons (TrpTrp vs. ArgArg, OR = 2.209, 95%CI 1.398-2.945), no significant link was found on subgroup analysis stratified by ethnicity. With regard to the Arg280His polymorphism, no significant association was found in each comparison. No particular study was found to significantly influence the pooled results, and no potential publication bias was detected. Conclusions: This meta-analysis suggested that the XRCC1 Arg399Gln polymorphism is moderately associated with increased risk of gliomas in Asians, while Arg194Trp and Arg280His polymorphisms demonstrated no significant influence. Due to the limited studies and the potential confounders, further studies are needed to confirm these results.

• Asian-Australasian Journal of Animal Sciences
• /
• v.30 no.8
• /
• pp.1175-1182
• /
• 2017

Objective: To create genetically modified goat as a biopharming source of recombinant human lacotoferrin (hLF) with transcription activator-like effector nucleases. Methods: TALENs and targeting vector were transferred into cultured fibroblasts to insert hLF cDNA in the goat beta-lactoglobulin (BLG) locus with homology-directed repair. The gene targeted efficiency was checked using sequencing and TE7I assay. The bi-allelic gene targeted colonies were isolated and confirmed with polymerase chain reaction, and used as donor cells for somatic cell nuclear transfer (SCNT). Results: The targeted efficiency for BLG gene was approximately 10%. Among 12 Bi-allelic gene targeted colonies, five were used in first round SCNT and 4 recipients (23%) were confirmed pregnant at 30 d. In second round SCNT, 7 (53%), 4 (31%), and 3 (23%) recipients were confirmed to be pregnant by ultrasound on 30 d, 60 d, and 90 d. Conclusion: This finding signifies the combined use of TALENs and SCNT can generate biallelic knock-in fibroblasts that can be cloned in a fetus. Therefore, it might lay the foundation for transgenic hLF goat generation and possible use of their mammary gland as a bioreactor for large-scale production of recombinant hLF.

• KSBB Journal
• /
• v.15 no.4
• /
• pp.331-336
• /
• 2000

The antimutagenic activity of the extract of Artemisia capillaris THUNB on the mutagenicity induced by benzo(a)pyrene [B(a)P] in the presense of S9 mixture was studied using bacterial mutagenic assay system. Samples harvested in summer and autumn were extracted using ethanol and hot water. Among these extracts the water extract of summer sample had the strongest inhibitory effect against the mutagenenicity of B(a)P, The water extract of Artemisia capillaris THUNB was separated again into ethanol soluble and insoluble parts. The ethanol insoluble part(El) of water extract exhibited higher inhibition effects than the ethanol soluble part against the mutagenic activity of B(a)P. El showed dose-dependent activity on the mutagenicity of B(a)P in SOS Chromotest and Ames test. The 50% inbibition concentraction $(IC_{50}$ of El were $200{\mu}g/assay$ $600{\mu}g/plate$ and $800{\mu}b/plate$ in E. coil PQ37 S. typhimurium TA100 and TA98 respectively. El were showed desmutagenic effect but had no effect on the DNA repair system for B(a)P-induced mutagenesis. HPLC analysis showed that the formation of aflatoxin M1 by cytochrome P-450 1A1 known as playing an impotant role on B(a) P-induced mutagenicity was highly inhibited by El. Therefore we encluded that B(a)P-induced mutagencity can be reduced possible due to the interference of el with cytochrome P-450 1A1-dependent bioactivation.

• The Korean Journal of Physiology and Pharmacology
• /
• v.13 no.3
• /
• pp.229-239
• /
• 2009

The aim of the present study was to examine the effect of provinol, which is a mixture of polyphenolic compounds from red wine, on the secretion of catecholamines (CA) from isolated perfused rat adrenal medulla, and to elucidate its mechanism of action. Provinol (0.3 ${\sim}$ 3 ${\mu}g/ml$) perfused into an adrenal vein for 90 min dose- and time-dependently inhibited the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (a direct membrane-depolarizer, 56 mM), DMPP (a selective neuronal nicotinic $N_N$ receptor agonist, 100 ${\mu}M$) and McN-A-343 (a selective muscarinic $M_1$ receptor agonist, 100 ${\mu}M$). Provinol itself did not affect basal CA secretion. Also, in the presence of provinol (1 ${\mu}g/ml$), the secretory responses of CA evoked by Bay-K-8644 (a voltage-dependent L-type dihydropyridine $Ca^{2+}$ channel activator, 10 ${\mu}M$), cyclopiazonic acid (a cytoplasmic $Ca^{2+}$-ATPase inhibitor, 10 ${\mu}M$) and veratridine (an activator of voltage-dependent $Na^+$ channels, 10 ${\mu}M$) were significantly reduced. Interestingly, in the simultaneous presence of provinol (1 ${\mu}g/ml$) plus L-NAME (a selective inhibitor of NO synthase, 30 ${\mu}M$), the CA secretory responses evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyclpiazonic acid recovered to the considerable extent of the corresponding control secretion in comparison with the inhibition of provinol-treatment alone. Under the same condition, the level of NO released from adrenal medulla after the treatment of provinol (3 ${\mu}g/ml$) was greatly elevated in comparison to its basal release. Taken together, these data demonstrate that provinol inhibits the CA secretory responses evoked by stimulation of cholinergic (both muscarinic and nicotinic) receptors as well as by direct membrane-depolarization from the perfused rat adrenal medulla. This inhibitory effect of provinol seems to be exerted by inhibiting the influx of both calcium and sodium into the rat adrenal medullary cells along with the blockade of $Ca^{2+}$ release from the cytoplasmic calcium store at least partly through the increased NO production due to the activation of nitric oxide synthase.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.4
• /
• pp.1325-1331
• /
• 2012

Tumor formation and growth is dictated by a very small number of tumor cells, called cancer stem cells, which are capable of self-renewal. The genesis of cancer stem cells and their resistance to conventional chemotherapy and radiotherapy via mechanisms such as multidrug resistance, quiescence, enhanced DNA repair abilities and anti-apoptotic mechanisms, make it imperative to develop methods to identify and use these cells as diagnostic or therapeutic targets. Aldehyde dehydrogenase 1 (ALDH1) is used as a cancer stem cell marker. In this study, we evaluated ALDH1 expression in CaSki, HeLa and SiHa cervical cancer cells using the Aldefluor method to isolate ALDH1-positive cells. We showed that higher ALDH1 expression correlated with significantly higher rates of cell proliferation, microsphere formation and migration. We also could demonstrate that SiHa-ALDH1-positive cells were significantly more tumorigenic compared to SiHa-ALDH1-negative cells. Similarly, SiHa cells overexpressing ALDH1 were significantly more tumorigenic and showed higher rates of cell proliferation and migration compared to SiHa cells where ALDH1 expression was knocked down using a lentivirus vector. Our data suggested that ALDH1 is a marker of cervical cancer stem cells and expand our understanding of its functional role.

• The Journal of Korean Obstetrics and Gynecology
• /
• v.23 no.2
• /
• pp.38-56
• /
• 2010

Purpose: This study was designed to evaluate the effect of administration of Foeniculi Fructus on ovarian functions and differential gene expressions related cell viability such as caspase-3, MAPK and MPG in female mice. Methods: We administered the Foeniculi Fructus to 6-week-old female CF-1 mice for 4, 8, 12 days. After administration of Foeniculi Fructus with 0.1, 1, 10, $100\;mg/m{\ell}$ concentration in the comparison of control group with $0\;mg/m{\ell}$, we observed the mean number of total ovulated oocytes and the number of morphologically normal oocytes. After entosomatic fertilization, we observed the rate of fertilized 2-cell embryos to blastocyst stage in vitro. Also we chose the caspase-3 for cell apoptosis, MAPK and MPG genes for cell viability and DNA repair by RT-PCR. Results: 1. In case of 4, 8, 12day administration of Foeniculi Fructus with 0.1, 1, 10, $100\;mg/m{\ell}$, the mean number of total ovulated oocytes and the number of morphologically normal oocytes were increased in the comparison of control group. 2. In case of 4, 8, 12day administration of Foeniculi Fructus with 0.1, 1, 10, $100\;mg/m{\ell}$, the rates of blastocyst formation from 2-cell stages were increased in the comparison of control group. 3. In case of 4, 8, 12day administration of Foeniculi Fructus with 0.1, 1, 10, $100\;mg/m{\ell}$, the gene expression of caspase-3, MAPK, MPG didn't show significant result in the comparison of control group. Conclusion: This study shows that Foeniculi Fructus has significant effects on the increase of the function on ovulation and embryonic development of female mice. But this results have nothing to do with caspase-3, MAPK and MPG genes. So we need a further study for which genes are related to the activation of reproductive functions of Foeniculi Fructus.