• 한국식품영양과학회지
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• 제26권3호
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• pp.528-533
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• 1997

This study was undertaken to determine the antimutagenic effects of Synurus deltoides extracts on the mutagenesis induced by 3-amino-1, 4-dimethyl-5-H-pyrido[4, 3-blindol(Trp-P-1), 2-amitnofluorene (2-AF) and 4-nitroquinolin-1-oxide(4NQO) using Ames test. Raw juice, heated juice, and ethanol extract from Synurus deltoides itself did not induce mutagenesis. The raw juice, heated juice and ethanol extract of 50${mu}ell$/plate showed approximately 90%, 37% and 28% inhibitory effect on the mutagenesis induced by Trp-P-1 against TA98 strain, while 80%, 60% and 58% inhibition was observed on the mutagenesis induced by 2-AF at the concentration of 200${mu}ell$/plate, respectively. TA100 strain was more sensitive than TA98 strain by raw juice, heated juice and ethanol extract on the mutagenesis induced by Trp-P-1 and 2-AF. Meanwhile, the raw juice, heated juice, and ethanol extract showed very limited inhibitory effects on the mutagenesis induced by 4-NQO against TA98 and TA100 strain. These results indicate that raw juice had the strongest inhibitory effect on the Trp-P-1 or 2-AF induced mutagenesis, but all of the extracts had a little antimutagenc effects on the 4-NQO induced mutagenesis.

• 생명과학회지
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• 제11권5호
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• pp.432-438
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• 2001

우리나라 동치미 발효에 관여하는 유산균의 항돌연변이활성을 조사하기 위하여 숙성중의 동치미부터 300여주의 유산균을 분리하였다. 이들 균주들의 항돌연변이활성이 활성을 Salmonella enterotica serovar typhimurium TA100과 TA98을 이용하여 조사하고 직접 변이원 MNNG, NPD, 4-NQO와 간접변이원으로서 AFB1에 대하여 항돌연변이 활성이 가장 우수한 DLAB19균주를 최종 선별하였다. 최종 선별한 DL-AB19의 형태학적, 배양학적 및 생리학적 특성을 조사하여 Bergeys Manual Systematic Bacteriology의 분류 기준에 따라 동정한 결과 Leuconostoc mesenteroides subsp. cremoris 또는 그 유연균으로 동정하였다. Leu. mesenteroides subsp. cremoris DLAB19의 배양 상징액의 MNNG, NPD, 4-NQO 및 AFB1에 대한 항돌연변이 활성은 100$\mu$ι/plate 첨가시활성이 가장 높게 나타났다. 또한 B. subtilis의 포자를 이용한 spore-assay 방법을 사용하여 MNNG와 4-NQO에 대한 항돌연변이 활성을 가지고 있음을 재확인하였다.

• 한국식품영양과학회지
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• 제33권6호
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• pp.930-935
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• 2004

Ames test와 SOS chromotest를 이용하여 유기 게르마늄과 게르마늄을 첨가하여 재배한 콩나물의 항돌연변이 효과를 검토하였다. 균주 Salmonella typhimurium TA100에서 AFB$_1$에 의하여 유발된 돌연변이는 Ge-132와 게르마늄 가루에 의하여 농도 의존적으로 저해 효과가 높게 나타났으며, 특히 유기 게르마늄을 20 mg/plate 첨가하였을 때 대조군에 비하여 87%의 돌연변이 유발 억제율을 나타내었다. 똑같은 실험계에서 게르마늄을 첨가하여 재배한 콩나물의 즙액과 methanol 추출물은 수돗물로 재배한 콩나물에 비하여 돌연변이 유발억제 작용이 유의적으로 높게 나타났다. 또한 직접돌연변이원인 MNNG와 4-NQO에 의해 유발된 돌연변이는 일반콩나물의 즙액을 200 $\mu$L/plate 첨가하였을 때 각각 37∼39%, 38∼48%의 저해효과를 나타낸 반면 같은 농도에서 게르마늄 콩나물의 즙액은 61%와 75%의 억제율을 나타내어 게르마늄 첨가 콩나물은 간접 돌연변이원뿐만 아니라 직접 돌연변이원에 의해서 유발된 돌연변이도 억제함을 알 수 있었다. 한편 E. coli PQ37 균주를 사용한 SOS chromotest에서 유기 게르마늄은 사용된 농도의 증가에 따라 돌연변이 유발억제작용이 증가하였으며, 게르마늄 콩나물의 methanol 추출물은 일반 콩나물에 비하여 높은 돌연변이 유발 억제작용을 나타내었다. 따라서 Ames test와 SOS chromotest를 통하여 게르마늄을 첨가하여 재배한 콩나물은 수돗물로 재배한 콩나물에 비하여 항돌연변이 효과가 우수한 것을 알 수 있었다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2349-2354
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• 2013

NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T gene polymorphisms have been reported to influence the risk for digestive tract cancer (DTC) in many studies; however, the results remain controversial and ambiguous. We therefore carried out a meta-analysis of published case-control studies to derive a more precise estimation of any associations. Electronic searches were conducted on links between this variant and DTC in several databases through April 2012. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of associations in fixed or random effect models. Heterogeneity and publication bias were also assessed. A total of 21 case-control studies were identified, including 6,198 cases and 7,583 controls. Overall, there was a statistically significant association between the NQO1 C609T polymorphism and DTC risk (TT vs. CC: OR=1.224, 95%CI=1.055-1.421; TT/CT vs. CC: OR=1.195, 95%CI=1.073-1.330; TT vs. CT/CC: OR=1.183, 95%CI=1.029-1.359; T vs. C: OR=1.180, 95%CI=1.080-1.290). When stratified for tumor location, the results based on all studies showed the variant allele 609T might have a significantly increased risk of upper digest tract cancer (UGIC), but not colorectal cancer. In the subgroup analysis by ethnicity, we observed a significantly risk for DTC in Caucasians. For esophageal and gastric cancer, a significantly risk was found in both populations, and for colorectal, a weak risk was observed in Caucasians, but not Asians. This meta-analysis suggested that the NQO1 C609T polymorphism may increase the risk of DTC, especially in the upper gastric tract.

• Journal of Microbiology and Biotechnology
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• 제25권10호
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• pp.1680-1686
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• 2015

Inhibition of 4-nitroquinoline-1-oxide (4-NQO) genotoxicity by a probiotic strain of Lactobacillus rhamnosus (IMC501) was assessed by the prokaryotic short-term bioassay SOSChromotest, using Escherichia coli PQ37 as the target organism. Results showed the ability of strain IMC501 to rapidly and markedly counteract, in vitro, the DNA damage originated by the considered genotoxin. The inhibition was associated with a spectroscopic hypsochromic shift of the original 4-NQO profile and progressive absorbance increase of a new peak. IR-Raman and GC-MS analyses confirmed the disappearance of 4-NQO after contact with the microorganism, showing also the absence of any genotoxic molecule potentially available for metabolic activation (i.e., 4-hydroxyaminoquinoline-1-oxide and 4-nitrosoquinoline-1-oxide). Furthermore, we have shown the presence of the phenyl-quinoline and its isomers as major non-genotoxic conversion products, which led to the hypothesis of a possible pattern of molecular transformation. These findings increase knowledge on lactobacilli physiology and contribute to the further consideration of antigenotoxicity as a nonconventional functional property of particular probiotic strains.

• 한국식품조리과학회지
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• 제14권5호
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• pp.468-474
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• 1998

This study was performed to determine the effects of antimutagenicity from Barley (Hordeum vulgare). In Salmonella typhimurium reversion assay (In vitro test), the extract of Barley (Hordeum vulgare) inhibited mutagenic activity of 4-NQO and Trp-p-1 with 59 mix. in Salmonella typhimurium TA98 and TA100. In Micronucleus test (In vivo test), the methanol extract of Barley (Hordeum vulgare) inhibited micronucleus formation in bone marrow by cyclophosphamide. The $\beta$-glucan of Barley (Hordeum vulgare) showed inhibitory effects of 59-77% in mutagenic activity of 4-NQO by Salmonella typhimurium TA100. The mutagenicity of Trp-p-1 with S9 mix. by Salmonella typhimurium TA98 showed inhibitory effects of 24-56%. The methanl extract (M) was fractionated with ether (MI), ethylacetate (M2), buthanol (M3) and water (M4). The Antimutagenicity of Trp-p-1 with 59 mix. by Salmonella typhimurium TA98 in Barley fraction showed the following: methanol extract (99.58%)>ether fraction (98.05%)>buthanol fraction (56.90%)>water fraction (56.72%)>ethyl acetate fraction (28.72%). Among them, ether fraction in TA 98 showed strong antimutagenicity effects (85.56%, 98.05%) against mutation induced by 4-NQO and Trp-p-1. As concentration of the methanol extract increased (1.25~5 g/kg/10 cc), micronucleus formation in bone marrow by chemical mutagen (CP) showed inhibitory effects of 50% (p< 0.05).

• 한국식품영양과학회지
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• 제21권2호
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• pp.143-148
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• 1992

아플라톡신 B$_1$과 4-NQO의 돌연변이 유발성에 미치는 녹황색 채소류의 메탄올 추출물과 쥬스들의 항돌연변이 효과를 검토하였다. Salmonella typhimurium TA98과 TA100을 이용한 Ames실험계를 사용하였는데 아플라톡신 B$_1$에 대해 채소류의 메탄올 추출물 중에는 들깻잎, 상치, 브로콜리, 쑥갓, 미나리, 들미나리, 붉은고추, 고추잎, 비름, 시금치, 무 등이 큰 항돌연변이성을 나타내었다 (p< 0.01). 이 경우 시험시료 중 약 50% 정도가 저해 효과를 나타내었지만, direct mutagen인 4-NQO에서는 실험 시료 27종중 25종류(93%)에서 항돌연변이성이 관찰되었다 (p<0.01, 0.05). 이중 60%이상 저해효과를 나타낸 시료는 양배추, 케일, 상치, 브로콜리, 갓, 풋고추, 피망, 시금치, 비름, 콩나물, 애호박이었다. 한편 쥬스로 부터 아플라톡신 B$_1$에 대해 항돌연변이 효과를 나타낸 채소류는 들깻잎, 들미나리, 시금치, 양배추로써 각각 용량 의존적으로 (50~500${\mu}\ell$/plate)농도의 증가에 따라 그 저해도가 크게 증가하였다. 한편 오이와 당근은 농도를 높여도 큰 저해효과는 관찰되지 않았다.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 2003년도 정기총회 및 학술발표회
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• pp.80-80
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• 2003

${\beta}$-lapachone(${\beta}$-Lap), a natural o-naphthoquinone, presents in the bark of the Lapacho tree. ${\beta}$-Lap is cytotoxic against a variety of human cancer cells and it potentiates the anti-tumor effect of Taxol. In addition, ${\beta}$-Lap has been reported to radiosensitize cancer cells by inhibiting the repair of radiation-induced DNA damage.In the present study, we investigated the cytotoxicity of ${\beta}$-Lap against RKO human colorectal cancer cells as well as the combined effect of ${\beta}$-LaP and ionizing radiation. An incubation of RKO cells with 5 ${\mu}$M of ${\beta}$-Lap for 4 h killed almost 90％ of the clonogenic cells. An incubation of RKO cells with 5 ${\mu}$M of ${\beta}$-Lap for 4 h or longer also caused massive apoptosis. Unlike other cytotoxic agents, ${\beta}$-Lap did not increase the expression of p53 and p21 and it suppressed the NFkB expression. The expression of Caspase 9 and 3 was minimally altered by ${\beta}$-Lap. Radiation and ${\beta}$-Lap acted synergistically in inducing clonogenic cell death and apoptosis in RKO cells when ${\beta}$-Lap treatment was applied after but not before the radiation exposure of the cells. Interestingly, a 4 h treatment with 5 ${\mu}$M of ${\beta}$-Lap starting 5 h after irradiation was as effective as that starting immediately after irradiation. The mechanisms of ${\beta}$-Lap-induced cell killing is controversial but a recent hypothesis is that ${\beta}$-Lap is activated by NAD(P)H: quinone-onidoreductase (NQO1) in the cells followed by an elevation of cytosolic Ca$\^$2+/ level and activation of proteases leading to apoptosis. It has been reported that NQO1 level in cells is markedly up-regulated for longer than 10 h after irradiation. Indeed, using immunological staining of NQO1, we observed a significant elevation of NQO1 expression in RKO cells 5h after 2-4 Gy irradiation. Such a prolonged elevation of NQO1 level after irradiation may be the reasons why the ${\beta}$-Lap treatment applied S h after irradiation was as effective as that applied immediately after irradiation in killing the cells. In view of the fact that the repair of radiation-induced damage is usually completed within 1-2 h after irradiation, it is highly likely that the ${\beta}$-Lap treahment applied 5 h after irradiation could not inhibit the repair of radiation-induced damage. For in vivo study, RKO cells were injected S.C. into the hind-leg of Nu/Nu mice, and allowed to grow to 130 mm3 tumor. The mice were i.p. injected with ${\beta}$-lapachone or saline 2 h after irradiation of tumors with 10 Gy of X-rays. The radiation induced growth delay was increased by 2.4 $\mu\textrm{g}$/g of ${\beta}$-lapachone. Taken together, we may conclude that the synergistic interaction of radiation and ${\beta}$-Lap in killing cancer cells is not due to radiosensitization by ${\beta}$-Lap but to an enhancement of ${\beta}$-Lap cytotoxicity by radiation through an upregulation of NQO1. The fact that NQO1 is elevated in tumors and that radiation causes prolonged increase of the NQO1 expression may be exploited to preferentially kill tumor cells using ${\beta}$-Lap in combination with radiotherapy.

• Biomolecules & Therapeutics
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• 제31권6호
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• pp.648-654
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• 2023

Oxidative stress-induced melanocyte apoptosis is linked to the immune system and plays a critical role in the pathogenesis of vitiligo. Aquaporin-3 (AQP3), which is downregulated in vitiligo keratinocytes, regulates intracellular H₂O₂ accumulation. However, the role of AQP3 in oxidative stress is uncertain in vitiligo. This study investigated the effect of downregulated AQP3 on oxidative stress in vitiligo using lesional and non-lesional skin specimen sets from vitiligo patients and primary cultured adult normal human epidermal keratinocytes, with or without downregulation and overexpression of AQP3 in the presence or absence of H₂O₂ treatment. The levels of nuclear factor E2-related factor 2 (NRF2) and/or its main target, NAD(P)H quinone dehydrogenase 1 (NQO-1), were lower in the lesional keratinocytes and cultured keratinocytes with AQP3 knockdown, but were increased in keratinocytes upon AQP3 overexpression. Ratios of NRF2 nuclear translocation and NQO-1 expression levels were further reduced in AQP3-knockdown keratinocytes following H₂O₂ treatment. The conditioned media from AQP3-knockdown keratinocytes treated with H₂O₂ contained higher concentrations of reactive oxygen species (ROS). Moreover, the number of viable melanocytes was reduced when the conditioned media were added to the culture media. Overall, AQP3 downregulation in the keratinocytes of patients with vitiligo can induce oxidative stress in neighboring melanocytes, leading to melanocyte death.

• 한국식품저장유통학회지
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• 제8권1호
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• pp.109-117
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• 2001

번데기동충하초(Cordyceps militaris(L. ex fr.) Link)의 수소전자공여능 및 항돌연변이원성을 살펴본 결과 부탄을 분획물과 에틸 아세테이트 분획물에서 수소전자공여능이 다른 시료에 비해 2배 이상 높게 나타났다. 항돌연변이원성 실험결과에서는 직접변이원인 MNNG, 4NQO 그리고 간접변이원인 B($\alpha$)P, Trp-P-1에 대해서 유의성 있는 돌연변이 억제효과를 보였다. MNNG(0.4 $\mu\textrm{g}$/plate)의 경우 S. typhimurium TA100 균주에서는 시료농도 200 $\mu\textrm{g}$/plate에서 에탄을 추출물이 78.1%인데 반해 부탄을, 물 분획물에서는 각각 90.4%와 87.6%로 매우 높은 억제효과가 나타났다. 4NQO(0.15 $\mu\textrm{g}$/plate)에 대한 S. typhymurium TA98 균주의 경우 에틸 아세테이트 분획물의 경우 80.4%였고, TA100 균주에서는 부탄을 분획물이 88.6%의 억제효과를 보였다. 또한 간접변이원의 경우 B($\alpha$)P(10 $\mu\textrm{g}$/plate)을 사용한 경우 에틸 아세테이트와 부탄을 분획물은 시료농도 200 $\mu\textrm{g}$/plate에서 85% 이상의 높은 억제율을 나타내었다. Trp-P-1(0.15 $\mu\textrm{g}$/plate)에서는 TA98 균주의 경우 200 $\mu\textrm{g}$/plate 농도에서 핵산 분획물과 부탄을 분획물이 각각 90.2%, 87.6%로 높은 억제율을 보여주었고, TA100 균주에 대해서는 에틸 아세테이트 분획물이 90.1%로 억제효과가 가장 높게 나타났다. 또한 같은 농도에서 부탄올과 물 분획물에서 각각 87.0%와 75.4%의 억제율을 나타내었다. 번데기동충하초 에탄을 추출물 및 분획물은 시료 농도증가에 따라 TA98과 TA100 균주 모두에서 각 변이원에 대한 돌연변이 억제효과도 증가하였다.