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The Effect of Pretreatment with Various Mutagens on Glycoconjugates of Plasma Membrane in HeLa Cells
Lee, Jong-Hwa,Oh, Kyu-Seon,Lee, Dong-Wook,Shin, Eun-Joo,Um, Kyung-Il Korean Environmental Mutagen Society 1998 한국환경성돌연변이·발암원학회지 Vol.18 No.2
본 연구는 돌연변이원인 자외선과 ethyl methanesulfonate(EMS) 그리고 bleomycin(BLM)을 전처리한 HeLa 세포에서 세포막에 존재하는 glycoconiugates에 미치는 이들 돌연변이원의 효과를 밝히기 위하여 세포생존 실험법과 Lectin cytochemistry법으로 조사하였다. 1 mM EMS를 전처리한 후 10 mM EMS를 처리한 군의 세포생존율은 10 mM EMS를 단독처리한 군의 세포생존율 보다 더 높았다. 그리고 10 mM EMS 단독처리군 보다 1 mM EMS를 전처 리 한 후 10 mM EMS를 처리한 군에서 Wheat germ agglutinin (WGA)은 더욱 강한 양성반응을 보였다. 반면에 succinylated wheat germ agglutinin (SWGA)는 10 mM EMS 단독처리군과 1 mM EMS를 전처리한 후 10mM EMS를 처리한 군에서 차이가 없었다. 이상의 결과들을 종합해 볼 때, HeLa세포에서 EMS에 대한 획득된 저항성은 다내약제성 또는 적응반응과 관련되는 원형질막의 sialic acid를 포함한 glycoconiugates와 관계 될 것으로 추측된다. The present investigation has been performed to elucidate the effect of pretreatment with low dose of ultraviolet radiation (UV), ethyl methansulfonate (EMS), and bleomycin (BLM) on cell survival and lectin-binding glycoconjugates of plasma membrane in HeLa cells treated with mutagen. The percentage of survival of cells pretreated with 1 mM EMS following treatment with 10 mM EMS was higher than that of cells treated with 10 mM EMS alone. Wheat germ agglutinin (WGA) staining intensity of cells pretreated with 1 mM EMS and subsequently treated with 10 mM EMS was stronger than that of cells treated with 10 mM EMS alone. But, succinylated wheat germ agglutinin (sWGA) staining intensity of cells pretreated with 1 mM EMS and subsequently treated with 10 mM EMS was similar to that of cells treated with 10 mM EMS alone. These results suggest that the acquired resistance to EMS is related to the glycoconjugates containing sialic acid of plasma membrane involved in multidrug resistance or adaptive response in HeLa cells.
Kang, Byung-Yong,Lee, Kang-Oh,Kim, Ki-Tae,Bae, Joon-Seol,Ryu, Jae-Chun,Kim, Jae-Hyoun,Lim, Seok-Rhin,Lee, Chung-Choo Korean Environmental Mutagen Society 2002 한국환경성돌연변이·발암원학회지 Vol.22 No.1
Essential hypertension is considered to be caused by a complicated combination of genetic and environmental factors. Alterations of lipid metabolism in plasma have been reported to be related to an increased risk of essential hypertension. The purpose of this study was to investigate the relationship between two genetic polymorphisms (Pvu II and Hind III RELPs) of the human lipoprotein lipase (LPL) gene and essential hypertension in korean population. In our result the Pvu II RFLP of LPL gene was significantly associated with essential hypertension (P < 0.05). Therefore, we suggest that the Pvu II RFLP of LPL gene may be useful as a genetic marker for essential hypertension in Korean population.
Lee Sun Mi,Choi Jin Hee Korean Environmental Mutagen Society 2005 한국환경성돌연변이·발암원학회지 Vol.25 No.1
In order to identify potential biomarkers of environmental monitoring, we evaluated heat shock genes expressions as effects of various environmental pollutants (nonylphenol, bisphenol-A, 17aethynyl estradiol, bis(2-ethylhexyl)phthalate, endosulfan, paraquat dichloride, chloropyriphos, fenitrothion, cadmium chloride, lead nitrate, potassium dichromate, benzo[a]pyrene and carbon tetrachloride) on larvae of aquatic midge Chironomus tentans (Diptera, Chironomidae). Heat shock protein 70 gene expression increased in most of chemicals treated larvae compared to control. The response was rapid and sensitive to low chemical concentrations but not stressor specific. In conjunction with stressor specific biomarkers, heat shock protein 70 gene expression in Chironomus might be developed for assessing exposure to environmental stressors in the fresh water ecosystem. Considering the potential of Chironomus larvae as biomonitoring species, heat shock gene expression has a considerable potential as a sensitive biomarker for environmental monitoring in Chironomus.
DNA Polymorphisms of the Human CYP11B2 and ${\gamma}$ Subunit of ENaC Genes in Korean Hypertensives
Kang, Byung-Yong,Bae, Joon-Seol,Kim, Ki-Tae,Lee, Kang-Oh Korean Environmental Mutagen Society 2002 한국환경성돌연변이·발암원학회지 Vol.22 No.4
Hypertension is characterized by multiple genetic and environmental factors. To establish the genetic basis of hypertension in Koreans, we investigated the genetic variations of two candidate genes (aldosterone synthase (CYP11B2), ${\gamma}$ subunit of the amiloride-sensitive epithelial sodium channel (ENaC) in the Korean patients with hypertension and normotensive controls. There were no significant differences in the genotype and allele frequencies between two groups, respectively. However, there was the significant difference between Korean and Caucasian populations in allele frequency of RFLPs in the two candidate genes. Therefore, these studies also need to be confirmed in other ethnic groups, although our results do not support a possible role of these genes on hypertension in Korean population
SNP Analysis of the Human LDL Receptor and CETP Gene in Korean Subjects with Hypertension
Shin, Jae-Hyun,Kang, Byung-Yong,Lee, Kang-Oh,Eo, Hyun-Shun,Bae, Joon-Seol,Kim, Ki-Tae,Kim, Hyun-Sup,Lee, Chung-Choo Korean Environmental Mutagen Society 2002 한국환경성돌연변이·발암원학회지 Vol.22 No.1
Essential hypertension is complex disorder influenced by multiple genetic and environmental factors. Alterations of lipid metabolism in plasma have been reported to be related to an increased risk of essential hypertension. The aim of this study was to investigate the relationship between two SNPs of the human LDL receptor and CETP gene and hypertension in Korean population. There were no significant differences in allele and genotype frequencies of two SNPs in normotensives and hypertensives. With respect to Hinc II RFLP in the LDL receptor gene, pooled odds ratio value indicated the significant heterogeneity among populations studied by meta-analysis (Breslow-Day test df = 2, P<0.05). In the case of Bam HI RFLP in the CETP gene,. our study is the first report of an association between the SNP of the CETP gene and hypertension, although our result failed to demonstrate the significant association between the Bam HI RFLP of the CETP gene and hypertension in Korean population. Further work, using larger sample sizes and various ethnic groups, is required to establish the precise role of these two candidate gene polymorphisms on hypertension.
A Bal I RFLP of Dopamine D3 Receptor Gene in Korean Hypertensives
Jang, Dai-Ho,Kim, Seoun-Jeong,Kang, Byung-Yong,Kim, Hyun-Hee,Lee, Kong-Oh Korean Environmental Mutagen Society 2003 한국환경성돌연변이·발암원학회지 Vol.23 No.1
Hypertension is characterized by multiple genetic and environmental factors. To establish the genetic basis of hypertension in Koreans, we investigated the genetic variations of dopamine D3 receptor (DRD3) gene in the Korean patients with hypertension and normotensive controls. There were no significant differences in the genotype and allele frequencies of Bal I RFLP in the DRD3 gene between two groups, respectively (P > 0.05). Our finding shows lack of association between a genetic marker of DRD3 gene and hypertension, suggesting that the genetic variation of DRD3 gene does not playa major role in the determination of hypertension in Korean population. Further studies in other ethnic groups will be required.
Kang, Il-Hyun,kim, Hyun-Jung,Oh, Hyeyoung,Park, Young-In,Dong, Mi-Sook Korean Environmental Mutagen Society 2003 한국환경성돌연변이·발암원학회지 Vol.23 No.3
Quercetin and naringenin are representative flavonoids that not only exert anti estrogenic, cholesterol-lowering and antioxidant activities but also can modulate the metabolism of many xenobiotics. The activity of the specific form(s) of CYP450 is likely to be a major determinant of susceptibility to chemically induced carcinogenesis between which varies among between individuals due to different dietary habits as well as genetic characteristics. People consume cooked meat or fish together with various vegetables containing substantial amounts of quercetin and naringenin that can modify the enzyme activity of CYP1A2 to stimulate or to inhibit the mutagenic activities of HCAs. Heterocyclic amines (HCAs) produced by cooking meat products at high temperatures are promutagens that are activated by cytochrome P450 (CYP) lA2. Using a newly developed Salmonella typhimurium TA1538/1A2bc-b5 strain, we tested the effect of quercetin and naringenin on the mutagenicity of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ). TA1538/1A2bc-b5 bears two plasmids, one expressing human CYP1A2 and NADPH-P450 reductase (NPR), and the other plasmid which expresses human cytochrome b5 (cyp b5). TA1538/1A2bc-b5 cells showed high activities of 7-ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD) associated with CYP1A2 and are very sensitive to mutagenesis induced by several HCAs. MeIQ was found to be the strongest mutagen among the HCAs tested in this system. Mutagenicity of MeIQ was enhanced 50 and 42% by quercetin at 0.1 and 1 mM, respectively, but suppressed 82% and 96% at 50 mM and 100 mM. Naringenin also increased the MeIQ-induced mutation about 37% and 22% at 0.1 and 1 mM, but suppressed it 32% and 63% at 50 mM and 100 mM concentrations, respectively, in TA 1538/1A2bc-b5 cells. Thus, they stimulated the MeIQ induced mutation at low concentrations, but strongly suppressed it at high concentrations. This biphasic effect of flavonoids was due to the stimulation or the inhibition of CYP1A2 activity in a dose-dependent manner judging by the activities of EROD or MROD in the Salmonella cells. Collectively, it is likely that the biphasic effects of quercetin and naringenin on the MeIQ-induced mutagenesis in S. typhimurium TA1538/CYP1A2bc-b5 were due to their differential modification of the CYP1A2 activity in these cells.
Kang, Byung-Yong,Bae, Joon-Seol,Kim, Jae-Hyoun,Om, Ae-Son,Ryu, Jae-Chun,Eo, Hyun-Seon,Shin, Jae-Hyun,Shin, Jung-Hee,Lee, Chung-Choo,Kim, Ki-Tae Korean Environmental Mutagen Society 2001 한국환경성돌연변이·발암원학회지 Vol.21 No.2
Essential hypertension is a heterogeneously multifactorial disease in which blood pressure is harmfully high without overt cause. Both genetic and environmental factors have been implicated in its etiology. In view of the regulatory role of this peptide in the carbohydrate metabolism and renin-angiotensin system, amylin gene has been proposed to a candidate gene for essential hypertension. Therefore, we scanned the amylin gene for mutations in 133 Korean normotensives and 61 essential hypertensives by single-strand conformational polymorphism, and found a single heterozygous S20G missense mutation. However, no significant difference was observed between normotensives and essential hypertensives in the distribution of allele and genotype frequencies of this mutation at the amylin gene (P>0.05). This finding suggests that S20G missense mutation of the amylin gene are unlikely to contribute to the etiology of essential hypertension in the Korean population.
Kang, Byung-Yong,Kim, Ki-Tae,Shin, Jung-Hee,Om, Ae-Son,Lee, Chung-Choo Korean Environmental Mutagen Society 2001 한국환경성돌연변이·발암원학회지 Vol.21 No.1
Essential hypertension is considered to be a multifactorial disease that is influenced not only by environmental factors but also by genetic factors. Genes involved in lipoprotein synthesis, modification and metabolism are candidates for essential hypertension. The purpose of this study was to estimate gene frequencies of paraoxonase/arylesterase (PON1) gene in Korean population and investigate the relationship between genotypes of this gene and essential hypertension or cardiovascular risk factors. In order to estimate the genotype frequencies, Alw I RFLP of PON1 gene was used as genetic marker. There were no significant differences in allele and genotype frequencies between normotensives and essential hypertensives, respectively. However, Alw I RELP of PON1 gene were significantly associated with plasma HDL-cholesterol level in Korean population (one-way ANOVA test, p=0.008). Therefore, our result suggest that this RFLP of PON1 gene may be protective marker on cardiovascular disease in Korean population.
Genetic Epidemiology of Renin-Angiotensin System in Korean Population
Kang, Byung-Yong,Bae, Joon-Seol,Kim, Ki-Tae,Oh, Ju-Hyung,Lee, Kang-Oh,Ryu, Jae-Chun,Kim, Jae-Hyoun,Oh, Sang-Duk,Yoon, Moon-Young,Lee, Chung-Choo Korean Environmental Mutagen Society 2002 한국환경성돌연변이·발암원학회지 Vol.22 No.1
Genetic polymorphisms of the renin-angiotensin system (RAS) have been associated with hypertension in various ethnic groups, but no relation between these polymorphisms and hypertension has yet been systematically evaluated. To assess the relationship between allelic variation of RAS genes and hypertension, we performed the case-control studies using genetic markers in Korean normotensives and hypertensives. The allele and genotype frequencies of RAS genes in Korean population were not significantly different between normotensives and hypertensives. To investigate the distribution of allele frequencies among various populations, the data obtained in this study were compared to those in other ethnic groups studied previously. Except for T174M polymorphism of angiotensinogen (AGT) gene, allele frequencies of RAS genes were different among racial groups. The reason for these differences may be due to the difference in various genetic or environmental background or due to the effects by various sample size studied. In addition, it can be emphasized that carefully designed studies are required to minimize the ethnic heterogeneity of the case and control populations.