• Environmental Mutagens and Carcinogens
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• v.19 no.2
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• pp.112-115
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• 1999

The action mechanism of the inhibitory effect of some natural products on the DNA strand break and DNA damage was investigated in vitro and in vivo. In the E. coli chromosomal DNA strand break experiment in vitro, three mushroom water extracts were effective on the DNA strand breaking by daunorubicin. Phellinus linteus water extract inactivated daunorubicin, a DNA strand breaking agent, but did not protect DNA from daunorubicin-induced DNA strand breaking. Agaricus blazei water extract inhibited DNA strand breaking action of daunorubicin not only by daunorubicin inactivation, but also by DNA protection from daunorubicin. An inhibitory effect of Ganoderma lucidum water extract on the DNA strand break was based on the DNA protection rather than daunorubicin inactivation. In vivo mutagen assay system (SOS-chromotest), among three mushroom water extracts Phellinus linteus water extract was the most effective one on the inhibition of DNA damage by 4-NQO. The results suggest that all three mushroom water extracts inhibit daunorubicin-induced DNA damage and in vivo DNA damaging action of 4-NQO by the reaction of mutagen inactivation or DNA protection from the mutagen.

• 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.16 no.5
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• pp.1821-1825
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• 2015

Background: Associations between the NQO1 C609T polymorphism and hepatocellular carcinoma (HCC) risk are a subject of debate. We therefore performed the present meta-analysis to evaluate links with HCC susceptibility. Materials and Methods: Several major databases (PubMed, EBSCO), the Chinese national knowledge infrastructure (CNKI) and the Wanfang database were searched for eligible studies. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the strength of associations. Results: A total of 4 studies including 1,325 patients and 1,367 controls were identified. There was a significant association between NQO1 C609T polymorphism and HCC for all genetic models (allelic model: OR=1.45, 95%CI=1.23-1.72, p<0.01; additive model: OR=1.96, 95%CI=1.57-2.43, p<0.01; dominant model: OR=1.62, 95%CI=1.38-1.91, p<0.01; and recessive model: OR=1.53, 95%CI=1.26-1.84, p<0.01). On subgroup analysis, similarly results were identified in Asians. For Asians, the combined ORs and 95% CIs were (allelic model: OR=1.50, 95%CI=1.24-1.82, p<0.01; additive model: OR=2.11, 95%CI=1.48-3.01, p<0.01; dominant model: OR=1.69, 95%CI=1.42-2.02, p<0.01; and recessive model: OR=1.59, 95%CI=1.16-2.19, p<0.01). Conclusions: The current meta-analysis suggested that the NQO1 C609T polymorphism could be a risk factor for developing HCC, particularly in the Chinese population.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6343-6348
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• 2012

Objective: The NAD(P)H:quinone oxidoreductase 1 (NQO1) rs1800566 polymorphism, leading to proline-toserine amino-acid and enzyme activity changes, has been implicated in bladder cancer risk, but individually published studies showed inconsistent results. We therefore here conducted a meta-analysis to summarize the possible association. Methods: A systematic literature search up to August 27, 2012 was carried out in PubMed, EMBASE and Wanfang databases, and the references of retrieved articles were screened. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were analyzed for homozygote contrast (TT vs. CC), additive model (T vs. C), dominant model (TT+CT vs. CC), and recessive model (TT vs. CC+CT) to assess the association using fixed- or random-effect models. Results: We identified 12 case-control studies including 3,041 cases and 3,128 controls for the present meta-analysis. Significant association between NQO1 rs1800566 genetic polymorphism and risk of bladder cancer was observed in the additive model (OR = 1.15, 95% CI = 1.01-1.30, p = 0.030). Moreover, in the subgroup analysis stratified by ethnicity, significant associations were observed in Asians (OR = 1.26, 95% CI = 1.08-1.47, p = 0.003 for T vs. C; OR = 1.68, 95% CI = 1.21-2.32, p = 0.002 for TT vs. CC; OR = 1.50, 95% CI = 1.13-1.98, p = 0.005 for TT vs. CT+CC) but not in Caucasians. Conclusions: The results suggest that NQO1 rs1800566 genetic polymorphism may contribute to bladder cancer development, especially in Asians.

• 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.

• 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.

• 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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.29 no.5
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• pp.881-887
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• 2000

The antimutagenic effects of persimmon leaf tea extract (PLTE) at concentration levels consumed by human were examined in mice using micronuleus induction with MMC(mitomycin C) or 4-NQO (4-nitroquinoline-1-oxide). When mice received oral gavage of 10 equivalent to PLTE 24 hr and 6 hr before, and 5 equivalent to PLTE 6 hr before and 3 hr after intraperitoneal injection of MMC, a significant decrease in the frequency of micronuclei were observed. The induction of micronuclei by 4-NQO was suppressed by oral dosage of PLTE at 5 equivalent to PLTE 6 hr before and 3 hr after, 10 equivalent to PLTE 3 hr before and 3 hr after intraperitoneal injection of MMC. Though the components of PLTE have not been analyzed so far, our present results suggest the existence of several bio-antimutagens and/or desmutagens in PLTE, beside catechin, well-known antimutagen.

• 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.