4 nitroquinoline 1 oxide

Summary

Summary: A potent mutagen and carcinogen. This compound and its metabolite 4-HYDROXYAMINOQUINOLINE-1-OXIDE bind to nucleic acids. It inactivates bacteria but not bacteriophage.

Top Publications

  1. Kanojia D, Vaidya M. 4-nitroquinoline-1-oxide induced experimental oral carcinogenesis. Oral Oncol. 2006;42:655-67 pubmed
    ..In the present review an attempt has been made to collate the information available on mechanisms of action of 4NQO, studies carried out for the development of biomarkers and chemopreventives agents using 4NQO animal models. ..
  2. Yoshida K, Tanaka T, Hirose Y, Yamaguchi F, Kohno H, Toida M, et al. Dietary garcinol inhibits 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in rats. Cancer Lett. 2005;221:29-39 pubmed
  3. Ribeiro D, Favero Salvadori D, da Silva R, Ribeiro Darros B, Alencar Marques M. Genomic instability in non-neoplastic oral mucosa cells can predict risk during 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis. Oral Oncol. 2004;40:910-5 pubmed
    ..Genomic instability appears to be associated with the risk and progression of oral cancer. ..
  4. Gannot G, Buchner A, Keisari Y. Interaction between the immune system and tongue squamous cell carcinoma induced by 4-nitroquinoline N-oxide in mice. Oral Oncol. 2004;40:287-97 pubmed
    ..The interaction between the tumor and immune response components is important for diagnosis and treatment purposes. ..
  5. Tang X, Knudsen B, Bemis D, Tickoo S, Gudas L. Oral cavity and esophageal carcinogenesis modeled in carcinogen-treated mice. Clin Cancer Res. 2004;10:301-13 pubmed
    ..This model will also allow testing of cancer chemopreventive drugs in various transgenic mouse strains. ..
  6. Suzuki R, Kohno H, Suzui M, Yoshimi N, Tsuda H, Wakabayashi K, et al. An animal model for the rapid induction of tongue neoplasms in human c-Ha-ras proto-oncogene transgenic rats by 4-nitroquinoline 1-oxide: its potential use for preclinical chemoprevention studies. Carcinogenesis. 2006;27:619-30 pubmed
  7. Kaplan I, Hochstadt T, Dayan D. PCNA in palate and tongue mucosal dysplastic lesions induced by topically applied 4NQO in desalivated rat. Med Oral. 2002;7:336-43 pubmed
    ..The specific salivary component and the mechanism by which this protective effect is rendered are yet to be discovered. ..
  8. Schoop R, Baatenburg de Jong R, Noteborn M. Apoptin induces apoptosis in an oral cancer mouse model. Cancer Biol Ther. 2008;7:1368-73 pubmed
    ..The fact that apoptin induces apoptosis in primary squamous cell carcinoma cells indicates that apoptin is a potential therapeutic agent for treatment of head and neck squamous cell carcinoma...
  9. Demogines A, Smith E, Kruglyak L, Alani E. Identification and dissection of a complex DNA repair sensitivity phenotype in Baker's yeast. PLoS Genet. 2008;4:e1000123 pubmed publisher
    ..It also provides tools for understanding the effect of genetic background on sensitivity to genotoxic agents. ..

More Information

Publications62

  1. Niwa S, Ueno S, Shirasu R. Alteration of pRb expression in the development of rat tongue carcinoma induced by 4-nitroquinoline 1-oxide. Oral Oncol. 2001;37:579-85 pubmed
    ..The decrease of pRb in quantity and the increase of its phosphorylation may prevent G1 arrest and consequently accelerate proliferation of the chemically injured cells contributing to the initiation of carcinogenesis. ..
  2. Inoue T, Aikawa K, Tezuka H, Kada T, Shultz L. Effect of DNA-damaging agents on isolated spleen cells and lung fibroblasts from the mouse mutant "wasted," a putative animal model for ataxia-telangiectasia. Cancer Res. 1986;46:3979-82 pubmed
    ..We concluded that observed defects in DNA repair in wasted cells are not identical to those reported in human cells from ataxia-telangiectasia patients. ..
  3. Imaida K, Sato H, Okamiya H, Takahashi M, Hayashi Y. Enhancing effect of high fat diet on 4-nitroquinoline 1-oxide-induced pulmonary tumorigenesis in ICR male mice. Jpn J Cancer Res. 1989;80:499-502 pubmed
    ..The results thus indicate that dietary high fat can enhance 4NQO-induced lung tumorigenesis in mice. ..
  4. Vlckova V, Duhova V, Svidova S, Farkassová A, Kamasová S, Vlcek D, et al. Antigenotoxic potential of glucomannan on four model test systems. Cell Biol Toxicol. 2004;20:325-32 pubmed
  5. Jenkins G, Chaleshtori M, Song H, Parry J. Mutation analysis using the restriction site mutation (RSM) assay. Mutat Res. 1998;405:209-20 pubmed
    ..A later mutational peak, after the adduct level had declined, was assumed to be due to DNA sequence changes produced in the fibroblasts by the in vivo processing of DNA adducts. ..
  6. Makita H, Mutoh M, Maruyama T, Yonemoto K, Kobayashi A, Fujitsuka H, et al. A prostaglandin E2 receptor subtype EP1-selective antagonist, ONO-8711, suppresses 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis. Carcinogenesis. 2007;28:677-84 pubmed
  7. Yoshida S, Al Amodi H, Nakamura T, McInerny C, Shimoda C. The Schizosaccharomyces pombe cdt2(+) gene, a target of G1-S phase-specific transcription factor complex DSC1, is required for mitotic and premeiotic DNA replication. Genetics. 2003;164:881-93 pubmed
    ..These observations suggest that cdt2(+) plays an important role in DNA replication in both the mitotic and the meiotic life cycles of fission yeast. ..
  8. Sabouri N, Viberg J, Goyal D, Johansson E, Chabes A. Evidence for lesion bypass by yeast replicative DNA polymerases during DNA damage. Nucleic Acids Res. 2008;36:5660-7 pubmed publisher
    ..The nucleotide inserted opposite 8-oxoG is dATP. We propose that during DNA damage in S. cerevisiae increased dNTP concentration allows replicative DNA polymerases to bypass certain DNA lesions. ..
  9. Li C, Wang L, Wei Q. DNA repair phenotype and cancer susceptibility--a mini review. Int J Cancer. 2009;124:999-1007 pubmed publisher
    ..This finding needs additional validation by other investigators, and we also discussed issues in conducting this kind of research in the future. ..
  10. Tollefsen K, Bratsberg E, Bøyum O, Finne E, Gregersen I, Hegseth M, et al. Use of fish in vitro hepatocyte assays to detect multi-endpoint toxicity in Slovenian river sediments. Mar Environ Res. 2006;62 Suppl:S356-9 pubmed
  11. Beaudenon S, Huacani M, Wang G, McDonnell D, Huibregtse J. Rsp5 ubiquitin-protein ligase mediates DNA damage-induced degradation of the large subunit of RNA polymerase II in Saccharomyces cerevisiae. Mol Cell Biol. 1999;19:6972-9 pubmed
  12. Nakaune R, Adachi K, Nawata O, Tomiyama M, Akutsu K, Hibi T. A novel ATP-binding cassette transporter involved in multidrug resistance in the phytopathogenic fungus Penicillium digitatum. Appl Environ Microbiol. 1998;64:3983-8 pubmed
    ..These results suggested that the toxicant efflux system comprised of PMR1 participates directly in the DMI resistance of the fungus. ..
  13. Menichini P, Fronza G, Tornaletti S, Galiegue Zouitina S, Bailleul B, Loucheux Lefebvre M, et al. In vitro DNA modification by the ultimate carcinogen of 4-nitroquinoline-1-oxide: influence of superhelicity. Carcinogenesis. 1989;10:1589-93 pubmed
    ..Thus, these lesions must be considered as important DNA damage induced by Ac-4-HAQO. ..
  14. Schoop R, Noteborn M, Baatenburg de Jong R. A mouse model for oral squamous cell carcinoma. J Mol Histol. 2009;40:177-81 pubmed publisher
    ..Future survey of therapeutic options in the carcinogenic 4NQO model should be conducted around 40 weeks after the start of the treatment...
  15. Naoi K, Sunagawa N, Yoshida I, Morioka T, Nakashima M, Ishihara M, et al. Enhancement of tongue carcinogenesis in Hras128 transgenic rats treated with 4-nitroquinoline 1-oxide. Oncol Rep. 2010;23:337-44 pubmed
  16. Buscemi G, Carlessi L, Zannini L, Lisanti S, Fontanella E, Canevari S, et al. DNA damage-induced cell cycle regulation and function of novel Chk2 phosphoresidues. Mol Cell Biol. 2006;26:7832-45 pubmed
    ..These findings underscore the critical roles of S19, S33, and S35 and argue that these phosphoresidues may serve to fine-tune the ATM-dependent response of Chk2 to increasing amounts of DNA damage. ..
  17. Abraham S, Schupp N, Schmid U, Stopper H. Antigenotoxic effects of the phytoestrogen pelargonidin chloride and the polyphenol chlorogenic acid. Mol Nutr Food Res. 2007;51:880-7 pubmed
    ..In conclusion, the phytoestrogen PEL revealed antioxidative and antigenotoxic properties in HL-60 cells, but no significant additive interaction with the abundant nutritional polyphenol CLA under the tested conditions. ..
  18. Filho D, Pungartnik C, Cascardo J, Brendel M. Broken hyphae of the basidiomycete Crinipellis perniciosa allow quantitative assay of toxicity. Curr Microbiol. 2006;52:407-12 pubmed
    ..The pronounced sensitivity of the dikaryotic form of C. perniciosa to PAQ and H2O2 points to a weak protection from oxidative stress-inducing agents. ..
  19. Stang A, Witte I. Performance of the comet assay in a high-throughput version. Mutat Res. 2009;675:5-10 pubmed publisher
    ..For such applications the cost- and time-saving of the high-throughput method provides substantial advantages over the standard comet assay. ..
  20. Heltzel J, Maul R, Scouten Ponticelli S, Sutton M. A model for DNA polymerase switching involving a single cleft and the rim of the sliding clamp. Proc Natl Acad Sci U S A. 2009;106:12664-9 pubmed publisher
    ..Taken together, our findings challenge the toolbelt model and suggest instead that Pol IV contacts the rim of the clamp adjacent to the cleft that is bound by Pol III* before gaining control of the same cleft that is bound by Pol III*. ..
  21. Bardwell L, Burtscher H, Weiss W, Nicolet C, Friedberg E. Characterization of the RAD10 gene of Saccharomyces cerevisiae and purification of Rad10 protein. Biochemistry. 1990;29:3119-26 pubmed
    ..RAD10 cells (untransformed with the cloned gene) contain fewer than 500 molecules per cell. This is similar to the levels of the UvrA, UvrB, and UvrC nucleotide excision repair proteins in E. coli. ..
  22. Caldini G, Trotta F, Villarini M, Moretti M, Pasquini R, Scassellati Sforzolini G, et al. Screening of potential lactobacilli antigenotoxicity by microbial and mammalian cell-based tests. Int J Food Microbiol. 2005;102:37-47 pubmed
    ..Strain viability during and after genotoxin exposure was confirmed. Concordance of the results obtained with microbial and mammalian cell-based tests is underlined. ..
  23. Park K, Yang J, Choi Y, Lee C, Kim S, Byun Y. Chemoprevention of 4-NQO-induced oral carcinogenesis by co-administration of all-trans retinoic acid loaded microspheres and celecoxib. J Control Release. 2005;104:167-79 pubmed
  24. Chae S, Kafer E. uvsI mutants defective in UV mutagenesis define a fourth epistatic group of uvs genes in Aspergillus. Curr Genet. 1993;24:67-74 pubmed
    ..However, the uvsA mutation does not cause the defects in recombination and UV mutagenesis typical for this group. ..
  25. Diekmann M, Hultsch V, Nagel R. On the relevance of genotoxicity for fish populations I: effects of a model genotoxicant on zebrafish (Danio rerio) in a complete life-cycle test. Aquat Toxicol. 2004;68:13-26 pubmed
    ..9 microg/l displayed a significant reduction in egg production (P < 0.05). A mathematical simulation revealed that exposure to weak concentrations of NQO is leading to an elevated extinction risk. ..
  26. Sakamoto S, Nishikawa K, Heo S, Goto M, Furuichi Y, Shimamoto A. Werner helicase relocates into nuclear foci in response to DNA damaging agents and co-localizes with RPA and Rad51. Genes Cells. 2001;6:421-30 pubmed
    ..We propose that WRNp takes part in the homologous recombinational repair and in the processing of stalled replication forks. ..
  27. Mankouri H, Morgan A. The DNA helicase activity of yeast Sgs1p is essential for normal lifespan but not for resistance to topoisomerase inhibitors. Mech Ageing Dev. 2001;122:1107-20 pubmed
    ..g. functional interaction with topoisomerases), but essential for others (e.g. longevity). ..
  28. Mikulásová M, Kosikova B. Modulation of mutagenicity of various mutagens by lignin derivatives. Mutat Res. 2003;535:171-80 pubmed
    ..The antimutagenic effect of lignin samples varies with the method of isolation and modification, as well as with the genetic origin of the lignin. ..
  29. Lombard D, Beard C, Johnson B, Marciniak R, Dausman J, Bronson R, et al. Mutations in the WRN gene in mice accelerate mortality in a p53-null background. Mol Cell Biol. 2000;20:3286-91 pubmed
    ..Importantly, WRN(-/-);p53(-/-) mice show an increased mortality rate relative to WRN(+/-);p53(-/-) animals. We consider possible models for the synergy between p53 and WRN mutations for the determination of life span. ..
  30. Tsuda H, Iigo M, Takasuka N, Ueda S, Ohshima Y, Fukamachi K, et al. Possible enhancing activity of diacylglycerol on 4-nitroquinoline 1-oxide induced carcinogenesis of the tongue in human c-Ha-ras proto-oncogene transgenic rats. Food Chem Toxicol. 2007;45:1013-9 pubmed
    ..Tongue SCC induction of wild males and all females was not significant. The present results suggest that DAG oil may have enhancing and/or promotion potential for tongue carcinogenesis in male Tg featuring elevated ras expression. ..
  31. Vered M, Allon I, Buchner A, Dayan D. Stromal myofibroblasts and malignant transformation in a 4NQO rat tongue carcinogenesis model. Oral Oncol. 2007;43:999-1006 pubmed
    ..Defining the mechanism of evolvement of carcinoma-associated stromal myofibroblasts is expected to further broaden our knowledge on the micro-environmental events occurring during the malignant transformation. ..
  32. Zasukhina G, Vasil eva I, Durnev A, Gromov S, Fedorova O, Alfimov M. Antimutagenic activity of crown-containing compounds. Dokl Biol Sci. 2002;384:257-9 pubmed
  33. Nomura Y, Teshima W, Kawahara T, Tanaka N, Ishibashi H, Okazaki M, et al. Genotoxicity of dental resin polymerization initiators in vitro. J Mater Sci Mater Med. 2006;17:29-32 pubmed
    ..In comparison, 4NQO had strong genotoxicity, at 4 microM, roughly the same as that of BPO. Therefore, BPO should be used carefully in clinical dentistry. ..
  34. Suzuki R, Kohno H, Sugie S, Tanaka T. Dietary protocatechuic acid during the progression phase exerts chemopreventive effects on chemically induced rat tongue carcinogenesis. Asian Pac J Cancer Prev. 2003;4:319-26 pubmed
    ..001) during progression phase. Our results suggest that dietary PCA inhibits progression of 4-NQO-induced oral carcinogenesis, and such inhibition might be related to suppression of cell proliferation by PCA. ..
  35. Mohapatra R, Ramesh A, Jayaraman G, Santhiya S, Gopinath P. Modulatory action of 2-deoxy-D-glucose on mitomycin C-and 4-nitroquinoline-1-oxide-induced genotoxicity in Swiss albino mice in vivo. J Cancer Res Ther. 2009;5 Suppl 1:S53-6 pubmed publisher
    ..Incidence of micronucleated polychromatic erythrocytes (MnPCEs) induced by the mutagens were reduced up to 68%. 2-DG effectively reduces the MMC-and 4-NQO-induced genotoxicity. ..
  36. Yamamoto M, Reliene R, Oshima J, Schiestl R. Effects of human Werner helicase on intrachromosomal homologous recombination mediated DNA deletions in mice. Mutat Res. 2008;644:11-6 pubmed publisher
    ..This mouse model of WS in conjunction with different DNA damaging agents may provide insight into mechanisms of genomic instability, DNA repair, and carcinogenesis. ..
  37. Nakajima M, Kikuchi M, Saeki K, Miyata Y, Terada M, Kishida F, et al. Mutagenicity of 4-nitroquinoline 1-oxide in the MutaMouse. Mutat Res. 1999;444:321-36 pubmed
    ..01) in the 4NQO groups when compared with the vehicle control group by intraperitoneal treatment. Thus, these assay systems appeared to be of use in detecting not only genetic mutation but also chromosomal aberration. ..
  38. Suzuki T, Itoh S, Nakajima M, Hachiya N, Hara T. Target organ and time-course in the mutagenicity of five carcinogens in MutaMouse: a summary report of the second collaborative study of the transgenic mouse mutation assay by JEMS/MMS. Mutat Res. 1999;444:259-68 pubmed
  39. Fann Y, Metosh Dickey C, Winston G, Sygula A, Rao D, Kadiiska M, et al. Enzymatic and nonenzymatic production of free radicals from the carcinogens 4-nitroquinoline N-oxide and 4-hydroxylaminoquinoline N-oxide. Chem Res Toxicol. 1999;12:450-8 pubmed
    ..The above is consistent with a one-electron reduction in the metabolism of these nitro compounds to anion free radicals by various flavoenzyme reductases...
  40. Panigrahi G, Walker I. The N2-guanine adduct but not the C8-guanine or N6-adenine adducts formed by 4-nitroquinoline 1-oxide blocks the 3'-5' exonuclease action of T4 DNA polymerase. Biochemistry. 1990;29:2122-6 pubmed
    ..The N2-guanine adduct lies in the minor groove of the DNA double helix, while the other two adducts are found in the major groove. Apparently, only the former hinders progression of the enzyme. ..
  41. Wang B, Lu D, Jin L, Zheng W, Lou J, Deng H, et al. [Influence of 1.8 GHz microwave on DNA damage induced by 4 chemical mutagens]. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2005;23:163-6 pubmed
    ..05). However, MW did not enhance DNA damage induced by MMS and BLM (P > 0.05). Exposure to 1.8 GHz (SAR, 3 W/kg) microwave may not induce human lymphocyte DNA damage, but could enhance DNA damage induced by MMC and 4NQO. ..
  42. Peklak Scott C, Townsend A, Morrow C. Dynamics of glutathione conjugation and conjugate efflux in detoxification of the carcinogen, 4-nitroquinoline 1-oxide: contributions of glutathione, glutathione S-transferase, and MRP1. Biochemistry. 2005;44:4426-33 pubmed
    ..This result emphasizes the quantitative importance of enzyme-catalyzed conjugate formation, a crucial determinant of high-level, MRP-dependent protection of cells from NQO toxicity. ..
  43. Cenci G, Caldini G, Trotta F, Bosi P. In vitro inhibitory activity of probiotic spore-forming bacilli against genotoxins. Lett Appl Microbiol. 2008;46:331-7 pubmed publisher
    ..Although derived from an in vitro model, the results suggest that Bacillus-based probiotics could be useful for reducing the gastrointestinal risk originating from genotoxic agents. ..
  44. Chauvel Lebret D, Auroy P, Tricot Doleux S, Bonnaure Mallet M. Evaluation of the capacity of the SCGE assay to assess the genotoxicity of biomaterials. Biomaterials. 2001;22:1795-801 pubmed
  45. Arima Y, Nishigori C, Takeuchi T, Oka S, Morimoto K, Utani A, et al. 4-Nitroquinoline 1-oxide forms 8-hydroxydeoxyguanosine in human fibroblasts through reactive oxygen species. Toxicol Sci. 2006;91:382-92 pubmed
    ..This paper describes practical and sensitive ways to detect ROS and 8OHdG and discusses a new functional pathway to elicit genotoxicity. ..
  46. Valentin Severin I, Le Hegarat L, Lhuguenot J, Le Bon A, Chagnon M. Use of HepG2 cell line for direct or indirect mutagens screening: comparative investigation between comet and micronucleus assays. Mutat Res. 2003;536:79-90 pubmed
    ..2-AAF failed to induce DNA-damage in this assay. The present study shows that HepG2 cells could be a suitable tool for assessing the genotoxicity of direct and indirect mutagens and for establishing the lowest genotoxic concentration. ..
  47. Taguchi K, Tanaka Y, Imaeda T, Hirai M, Mohri S, Yamada M, et al. Development of a genotoxicity detection system using a biosensor. Environ Sci. 2004;11:293-302 pubmed
    ..Therefore, the false negative prevention function of a biosensor using the TL210ctl strain has been checked. These results show that our proposed system can correctly detect genotoxicants. ..
  48. Xia J, Lv N, Hong Y, Li C, Tao X, Chen X, et al. Increased expression of focal adhesion kinase correlates with cellular proliferation and apoptosis during 4-nitroquinoline-1-oxide-induced rat tongue carcinogenesis. J Oral Pathol Med. 2009;38:524-9 pubmed publisher
    ..959, P < 0.05). Our results implicated a role for FAK in oral carcinogenesis. Inhibition of FAK might be a potential novel treatment strategy in this disease. ..
  49. Miyaki M, Akamatsu N, Sato C, Utsunomiya J. Chemical and viral transformation of cultured skin fibroblasts from patients with familial polyposis coli. Mutat Res. 1988;199:399-414 pubmed
    ..The present results suggest that additional changes in morphologically transformed FPC fibroblasts are required for malignant transformation. ..
  50. Pitigala Arachchi A, Matthews J, Crane I, Scully C, Prime S. Ia+ epithelial dendritic cells during oral carcinogenesis in the rat. J Oral Pathol. 1988;17:138-44 pubmed
    ..The results indicate that treatment with 4NQO stimulates an increase in Ia+ EDC numbers which, although remaining higher than in controls, is not maintained within, or adjacent to, sites of neoplastic change. ..
  51. Vered M, Yarom N, Dayan D. 4NQO oral carcinogenesis: animal models, molecular markers and future expectations. Oral Oncol. 2005;41:337-9 pubmed
  52. Czerninski R, Amornphimoltham P, Patel V, Molinolo A, Gutkind J. Targeting mammalian target of rapamycin by rapamycin prevents tumor progression in an oral-specific chemical carcinogenesis model. Cancer Prev Res (Phila). 2009;2:27-36 pubmed publisher
  53. Karube T, Katayama H, Takemoto K, Watanabe S. Induction of squamous metaplasia, dysplasia and carcinoma in situ of the mouse tracheal mucosa by inhalation of sodium chloride mist following subcutaneous injection of 4-nitroquinoline 1-oxide. Jpn J Cancer Res. 1989;80:698-701 pubmed
    ..The NaCl inhalation is considered to have promotion-like action on the mouse tracheal mucosa after administration of 4-NQO injection. ..