• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7653-7658
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• 2015

Background: NAD(P)H:quinone oxidoreductase 1 (NQO1) is part of the antioxidant defence system involved in detoxification. This study aimed to analyze the influence of NQO1 (C609T) genetic polymorphism in non small cell lung cancer (NSCLC)as a putative risk factor. Materials and Methods: Present study included 100 cases of NSCLC (adenocarcinoma) patients and 100 age and sex matched healthy controls. NQO1 (C609T) genotyping was performed by allele specific PCR for assessment of putative associations with clinical outcome and genotypes of. The association of the polymorphism with the survival of NSCLC patients' was analyzed by Kaplan-Meier method. Results: In Indian NSCLC (adenocarcinoma) patients increased risk of developing NSCLC was found to be associated with NQO1 609TT genotype [OR 3.68(0.90-14.98), RR 2.04(0.78-5.31)] for CT [OR 2.91(1.58-5.34), RR 1.74(1.23-2.44) p=0.0005 for CT], for CT+TT [ OR 3.26(1.82-5.82), RR 1.87(1.34-2.61) p<0.0001 for CT+TT]. A significant difference (p=0.0009) was observed in genotype distribution among cases and healthy controls. Patients with CT+TT genotype exhibited a significant poor overall survival compared with patients displaying homozygous CC genotype (p=0.03) and when survival independently compared with CC, TT and CT genotype was also found to be significantly associated (p=0.02). Overall median survival times were CT 6.0 months, TT 8.2 months, and CT + TT (6.4 months)]. Conclusions: The present study revealed that NQO1 CT, TT and CT+TT genotypes may be associated with clinical outcome and risk of developing NSCLC in the Indian population.

• Korean Journal of Food Science and Technology
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• v.32 no.2
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• pp.417-423
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• 2000

Lactobacillus plantarum KLAB21 isolated from Kimchi has been reported to produce antimutagenic subtance(s) in the culture medium. In this study, antimutagenic effects of the strain KLAB21 were investigated to under various culture conditions maximize the production of antimutagenic substance(s) against N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) on Salmonella typhimurium TA100 and 4-nitroquinoline-1-oxide(NQO) on S. typhimurium TA98. Glucose(2%) as a carbon source and yeast extract(1%) as a nitrogen source resulted in the highest production of the antimutagenic substance(s) against both mutagens in the culture supernatant of L. plantarum KLAB21. The most effective concentrations of bactopeptone as a nitrogen source were 1% against MNNG and 1.5% against NQO. Optimal pH of the medium, culture temperature, and shaking speed for the antimutagenic substance(s) production were pH 7.0, $37^{\circ}C$ and 150 rpm, respectively. Under the optimal condition, the antimutagenic effects of L. plantarum KLAB21 culture supernatant were 98.4% against MNNG on S. typhimurium TA100 and 57.3% against NQO on S. typhimurium TA98.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5311-5316
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• 2013

A functional polymorphism in the NQO1 gene, featuring a 609C>T substitution,leading to proline to serine amino-acid and enzyme activity changes, has been implicated in cancer risk. However, individually published investigations showed inconclusive results, especially for leukemia. In this study, we therefore performed a meta-analysis of 21 publications with a total of 3,634 cases and 4,827controls, mainly for leukemia. We summarized the data on the association between the NQO1 609C>T polymorphism and risk of leukemia and performed subgroup analyses by ethnicity and leukemia type. We found that the variant TT homozygous genotype o was associated with a modestly increased risk of leukemia (TT versus CT/CC: OR=1.23, 95%CI=1.00-1.51, heterogeneity=0.76; $I^2$=0%). Following further stratified analyses, increased risk was only observed in subgroups of Caucasians. This meta-analysis suggests that the NQO1 609T allele is a high-penetrance risk factor for leukemia in Caucasians. The effect on leukemia may be modified by ethnicity and leukemia type, and the small sample sizes of the subgroup analyses suggest that further larger studies are needed.

• Archives of Pharmacal Research
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• v.24 no.5
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• pp.390-396
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• 2001

Synthesized 6-arylamino-5,8-quinolinediones 4a-4j and 6-chloro-7-arylamino-5,8-isoquinolinediones 5a-5g were evaluated for effects on NAD(P)H quinone oxidoreductase (NQOl ) activity with the cytosolic fractions derived from cultured human lung cancer cells and their cytotoxicity in cultured several human solid cancer cell lines. The 5,8-quinolinediones 4 and 5,8-isoquinolinediones 5 affected the reduction potential by NQO1 activity and showed a potent cytotoxic activity against human cancer cell lines. The tested compounds 4a, 5c, 5f, and 5g were considered as more potent cytotoxic agents. The compounds 4d, 5b, 5c, 5e and 5g were comparable modulators of NQO1 activity.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6403-6407
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• 2012

Detoxifying enzymes are present in most epithelial cells of the human gastrointestinal tract where they protect against xenobiotics which may cause cancer. Induction of examples such as glutathione S-transferase (GST) and its thiol conjugate, glutathione (GSH) as well as NAD(P)H: quinoneoxidoreductase (NQO1) facilitate the excretion of carcinogens and thus preventing colon carcinogenesis. Pterostilbene, an analogue of resveratrol, has demonstrated numerous pharmacological activities linked with chemoprevention. This study was conducted to investigate the potential of pterostilbene as a chemopreventive agent using the HT-29 colon cancer cell line to study the modulation of GST and NQO1 activities as well as the GSH level. Initially, our group, established the optimum dose of 24 hours pterostilbene treatment using MTT assays. Then, effects of pterostilbene ($0-50{\mu}M$) on GST and NQO1 activity and GSH levels were determined using GST, NQO1 and Ellman assays, respectively. MTT assay of pterostilbene ($0-100{\mu}M$) showed no cytotoxicity toward the HT-29 cell line. Treatment increased GST activity in the cell line significantly (p<0.05) at 12.5 and $25.0{\mu}M$. In addition, treatment at $50{\mu}M$ increased the GSH level significantly (p<0.05). Pterostilbene also enhanced NQO1 activity significantly (p<0.05) at $12.5{\mu}M$ and $50{\mu}M$. Hence, pterostilbene is a potential chemopreventive agent capable of modulation of detoxifiying enzyme levels in HT-29 cells.

• Journal of Life Science
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• v.5 no.3
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• pp.121-125
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• 1995

To determine whether the omega 3 family, linolenic acis(LnA) is effective to inhibit carcinogens/mutagens-induced mutagenesis, we employed the Ames test using Salmonella typhimurium strain of TA100 and the SOS chromotest using Escherichia coli PQ37 strain. The inhibitory effect of LnA shown in the Ames assaying system was 95%, 78% and 73% when the mutagenicities were mediated by AFB$_{1}$, MNNG and 4-NQO, respectively. LnA shows a strong antimutagenic activity against indirect mutagen of AFB$_{1}$, whereas the same concentration of LnA exhibited weaker inhibitory effects on the direct mutagen of MNNG and 4-NQO than that of AFB$_{1}$. However. LnA reduced more than 80% of SOS responses induced by MNNG and 4-NQO when the adding concentration increased to 5%. We conclude that LnA contains in vitro antimutagenic properties and that this finding warrants further investigation both in vitro and in vivo to assess its possible chemotherapeutic potential.

• Preventive Nutrition and Food Science
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• v.2 no.1
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• pp.29-34
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• 1997

In order to determine the effectiveness of linoleic acid(LA) to inhibit carcinogens/mutagens-induced mu-tagenesis, Ames test using Salmonella typhimurium TA100 and the SOS chromotest using E. Coli PQ37, were carried out. The inhibitory effect of LA(1%) on the Ames mutagenicity test were 98%, 78%and 69% mediated by aflatoxin B₁(AFB₁), N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) and 4-nitroquinoline-1-oxide(4-NQO), respectively. LA exhibited a strong antimutagenic activity aganist indirect mutagen, AFB₁whereas exhibited the same concentration of LA showed weaker inhibitory effects on direct mutagens of MNNG and 4-NQO than that AFB₁. LA also reduced the SOS responses induced by MNNG and 4-NQO significantly. This result showed a possibility that LA can be a protective agent in early step of cancinogenesis.

• Korean Journal of Food Science and Technology
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• v.30 no.2
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• pp.439-445
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• 1998

The antimutagenic activity of the water extract of Rehmannia glutinosa Liboschitz (RG) on the mutagenicity induced by 4-nitroquinoline 1-oxide (4-NQO), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), mitomycin C (MMC), $aflatoxin\;B_1\;(AFB_1)$ and benzo(a)pyrene [B(a)P] were studied using the SOS Chromotest with Escherichia coli PQ37. The water extract of RG was separated into methanol soluble and methanol insoluble parts. The methanol soluble part exhibited higher inhibition effects than the methanol insoluble part against the mutagenic activities of five mutagens. Step-wise fractionation of methanol soluble part was done using methanol, ethyl acetate and water. Among these fractions, water fraction had the strongest inhibitory effects against the mutagenenicity of five model mutagens, showing $4.5{\sim}29.5%$ inhibition, but the $AFB_1$ mutagenic potency was increased slightly by ethyl acetate fraction. The water fraction was further partitioned by sephadex LH-20 column chromtography, and 9 subfractions were obtained. The fraction III showed the strongest inhibitory effects with dose response against the mutagenic activities induced by all the tested chemical mutagens. The inhibition rates of fraction III at concentration of $400\;{\mu}g/assay$ were 29%, 35%, 38%, 25% and 24% against 4-NQO, MNNG, MMC, AFBl and B(a)P, respectively. The fraction III also exhibited a strong bio-an-timutagenicity against 4-NQO and $AFB_1$ by showing more than 40% inhibition.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.4
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• pp.410-415
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• 2008

This study was performed to observe the antimutagenic and cytotoxic activities of methanol extract of kochujang added with sea tangle and deep sea water salts (SDK) and kochujang added with sea tangle (SK) using the Ames test and SRB assay, respectively. The direct antimutagenic effect of SDK and SK methanol extracts were examined by Ames test using Salmonella Typhimurium TA98 and TA100. In the Ames test, methanol extract of SDK and SK alone did not exhibit mutagenicity and most of the samples showed high antimutagenic effects against mutation induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 4-nitroquinoline-1-oxide (4NQO). Methanol extract of SDK ($200{\mu}g$/plate) showed approximately 71.4% inhibitory effect on the mutagenesis induced by 4NQO against TA98 strain; whereas 56.1% and 83.6% inhibitions were observed on the mutagenensis induced by 4NQO and MNNG against TA100 strain. The cytotoxic effects of SDK and SK increased with increasing sample concentration against human cervical adenocarcinoma (HeLa), human hepatocellular carcinoma (Hep3B), human breast adenocarcinoma (MCF-7), human stomach adenocarcinoma (AGS), and human lung carcinoma (A549). The SDK at the concentration of 1 mg/ml showed cytotoxicities of 61.5%, 61.3%, 51.4%, 57.9% and 77.7% against HeLa, Hep3B, MCF-7, AGS and A549, respectively. In contrast 1 mg/ml treatment of SDK and SK methanol extract had only $2{\sim}38%$ cytotoxicity on human transformed primary embryonal kidney cell (293).

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2363-2367
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• 2014

The association between the NAD(P)H:quinone oxidoreductase 1 (NQO1) gene C609T polymorphism (rs1800566) and gastric cancer has been widely evaluated, but a definitive answer is so far lacking. We first conducted a case-control study to assess this association in a large Han Chinese population, and then performed a meta-analysis to further address this issue. Although our case-control association study indicated no significant difference in the genotype and allele distributions of C609T polymorphism between gastric cancer patients and controls, in the meta analysis involving 4,000 subjects, comparison of alleles 609T and 609C indicated a significantly increased risk (46%) for gastric cancer (95% confidence interval (95%CI) for odds ratio (OR)=1.20-1.79) in individuals with the T allele. The tendency was similar to the homozygote (OR=1.81, 95%CI: 1.16-2.84), dominant models (OR=1.41, 95%CI: 1.12-1.79), as well as recessive model (OR=1.58, 95%CI: 1.06-2.35). Stratified analysis by study design demonstrated stronger associations in population-based than in hospital-based studies. And ethnicity-based analysis demonstrated a significant association in Asians. We conclude that the NQO1 gene C609T polymorphism increases the risk for gastric cancer, especially in Asian populations.