Skip to main content
SpringerLink
Log in

Quercetin enhances tumorigenicity induced by N-ethyl-N′-nitro-N-nitrosoguanidine in the duodenum of mice

  • Original Article
  • Published:
Environmental Health and Preventive Medicine Aims and scope

Abstract

Quercetin, a flavonoid, widely distributed in many fruits and vegetables, is well known to have an antitumor effect despite its mutagenicity. In this study, we examined the effect of dietary quercetin on duodenum-tumorigenicity of mice induced by a chemical carcinogen, N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG). Eight-week-old male C57BL/6 mice were divided into 4 groups; ENNG without quercetin (group A), ENNG with 0.2% quercetin (group B), ENNG with 2% quercetin (group C), and 2% quercetin without ENNG (group D). ENNG was given in drinking water for the first 4 weeks, and thereafter quercetin was given in a mixed diet. At week 20, the average number of duodenal tumors per mouse was significantly higher in group C (mean±SE, 7.26±1.75, p<0.05) than in group A (2.32±0.31). The size of the duodenal tumors increased significantly in group B (1.79±0.09 mm, p<0.001) compared with group A (1.43±0.09 mm). In contrast, no duodenal tumor was induced in group D. The present findings suggest that excessive intake of quercetin occasionally is a risk factor for carcinogenesis of some specific organs such as the upper intestine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hacnszel W, Kurihara M, Segi M, Lee RKC. Stomach cancer among Japanese in Hawaii. J. Natl. Cancer Inst. 1972; 49: 969–988.

    Google Scholar 

  2. Graham S, Dayal H, Swanson M, Mittelman A, Wilkinson G. Diet in the epidemiology of cancer of the colon and rectum. J. Natl. Cancer Inst. 1978; 61: 709–714.

    PubMed  CAS  Google Scholar 

  3. Phillips RL. Role of life-style and dietary habits in risk of cancer among Seventh-Day Adventists. Cancer Res. 1975; 35: 3513–3522.

    PubMed  CAS  Google Scholar 

  4. Brown JP. A review of the genetic effects of naturally occurring flavonoids, anthraquinones and related compounds. Mutat. Res. 1980; 75: 243–277.

    PubMed  CAS  Google Scholar 

  5. Suolinna E-M, Buchsbaum RN, Racker E. The effect of flavonoids on aerobic glycolysis and growth of tumor cells. Cancer Res. 1975; 35: 1865–1872.

    PubMed  CAS  Google Scholar 

  6. Markaverich BM, Roberts RR, Alejandro MA, Johnson GA, Middleditch BS, Clark JH. Bioflavonoid interaction with rat uterine type II binding sites and cell growth inhibition. J. Steroid Biochem. 1988; 30: 71–78.

    Article  PubMed  CAS  Google Scholar 

  7. Yoshida M, Sakai T, Hosokawa N, Marui N, Matsumoto K, Fujioka A, Nishino H, Aoike A. The effect of quercetin on cell cycle progression and growth of human gastric cancer cells. FEBS Lett. 1990; 260: 10–13.

    Article  PubMed  CAS  Google Scholar 

  8. Hosokawa N, Hosokawa Y, Sakai T, Yoshida M, Marui N, Nishino H, Kawai K, Aoike A. Inhibitory effect of quercetin on the synthesis of a possibly cell-cycle-related 17-kDa protein, in human colon cancer cells. Int. J. Cancer 1990; 45: 1119–1124.

    Article  PubMed  CAS  Google Scholar 

  9. Ranelletti FO, Ricci R, Larocca LM, Maggiano N, Capelli A, Scambia G, Benedetti-Panici P, Mancuso S, Rumi C, Piantelli M. Growth-inhibitory effect of quercetin and presence of type-II estrogen-binding sites in human colon-cancer cell lines and primary colorectal tumors. Int. J. Cancer 1992; 50: 486–492.

    Article  PubMed  CAS  Google Scholar 

  10. Matsukawa Y, Nishino H, Okuyama Y, Matsui T, Matsumoto T, Matsumura S, Shimizu Y, Sowa Y, Sakai T. Effects of quercetin and/or restraint stress on formation of aberrant crypt foci induced by azoxymethane in rat colons. Oncology 1997; 54: 118–121.

    Article  PubMed  CAS  Google Scholar 

  11. Verma AK, Johnson JA, Gould MN, Tanner MA. Inhibition of 7,12-dimethylbenz(a)anthracene- andN-nitrosomethylurea-induced rat mammary cancer by dietary flavonol quercetin. Cancer Res. 1988; 48: 5754–5758.

    PubMed  CAS  Google Scholar 

  12. Nishino H, Iwashima A, Fujiki H, Sugimura T. Inhibition by quercetin of the promoting effect of teleocidin on skin papilloma formation in mice initiated with 7,12-dimethylbenz(a)anthracene. Gann 1984; 75: 113–116.

    PubMed  CAS  Google Scholar 

  13. Kato R, Nakadate T, Yamamoto S, Sugimura T. Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion and ornithine decarboxylase activity by quercetin: possible involvement of lipoxygenase inhibition. Carcinogenesis 1983; 4: 1301–1305.

    Article  PubMed  CAS  Google Scholar 

  14. Ambrose AM, Robbins DJ, DeEds F. Comparative toxicities of quercetin and quercitrin. J. Am. Pharm. Associ. Sci. Ed. 1952; 41: 119–122.

    CAS  Google Scholar 

  15. Bjeldanes LF, Chang GW. Mutagenic activity of quercetin and related compounds. Science 1977; 197: 577–578.

    Article  PubMed  CAS  Google Scholar 

  16. Carver JH, Carrano AV, MacGregor JT. Genetic effects of the flavonols quercetin, kaempferol, and galangin on Chinese hamster ovary cells in vitro. Mutat. Res. 1983; 113: 45–60.

    PubMed  CAS  Google Scholar 

  17. Pamukcu AM, Yalciner S, Hatcher JF, Bryan GT. Quercetin, a rat intestinal and bladder carcinogen present in bracken fern (Pteridium aquilinum). Cancer Res. 1980; 40: 3468–3472.

    PubMed  CAS  Google Scholar 

  18. Hirono I, Ueno I, Hosaka S, Takanashi H, Matsushima T, Sugimura T, Natori S. Carcinogenicity examination of quercetin and rutin in ACI rats. Cancer Lett. 1981; 13: 15–21.

    Article  PubMed  CAS  Google Scholar 

  19. Ito N, Hagiwara A, Tamano S, Kagawa M, Shibata M, Kurata Y, Fukushima S. Lack of carcinogenicity of quercetin in F344/DuCrj rats. Jpn. J. Cancer Res. 1989; 80: 317–325.

    PubMed  CAS  Google Scholar 

  20. Sugimura T, Fujimura S, Baba T. Tumor production in the glandular stomach and alimentary tract of the rat byN-methyl-N′-nitro-N-nitrosoguanidine. Cancer Res. 1970; 30: 455–465.

    PubMed  CAS  Google Scholar 

  21. Matsuyama M, Nakamura T, Suzuki H, Nagayo T. Morphogenesis of duodenal adenocarcinomas induced by N-ethyl-N′-nitro-N-nitrosoguanidine in mice and rats. Gann Monogr. Cancer Res. 1975; 17: 269–281.

    CAS  Google Scholar 

  22. Sunagawa M, Takeshita K, Nakajima A, Ochi K, Habu H, Endo M. Duration of ENNG administration and its effect on histological differentiation of experimental gastric cancer. Br. J. Cancer 1985; 52: 771–779.

    PubMed  CAS  Google Scholar 

  23. Ohgaki H, Hasegawa H, Kusama K, Morino K, Matsukura N, Sato S, Maruyama K, Sugimura T. Induction of gastric carcinomas in nonhuman primates byN-ethyl-N′-nitro-N-nitrosoguanidine. J. Natl. Cancer Inst. 1986; 77: 179–186.

    PubMed  CAS  Google Scholar 

  24. Nakamura T, Matsuyama M, Kishimoto H. Tumors of the esophagus and duodenum induced in mice by oral administration ofN-ethyl-N′-nitro-N-nitrosoguanidine. J. Natl. Cancer Inst. 1974; 52: 519–522.

    PubMed  CAS  Google Scholar 

  25. Kuhnau J. The flavonoids. A class of semi-essential food components: their role in human nutrition. World Rev. Nutr. Diet 1976; 24: 117–191.

    PubMed  CAS  Google Scholar 

  26. Hertog MGL, Hollman PCH, van de Putte B. Content of potentially anticarcinogenic flavonoids of tea infusions, wines, and fruit juices. J. Agric. Food. Chem. 1993; 41: 1242–1246.

    Article  CAS  Google Scholar 

  27. Ueno I, Nakano N, Hirono I. Metabolic fate of [14C] quercetin in the ACI rat. Jap. J. Exp. Med. 1983; 53: 41–50.

    PubMed  CAS  Google Scholar 

  28. Jones E, Hughes RE. Quercetin, flavonoids and the life-span of mice. Exp. Gerontol. 1982; 17: 213–217.

    Article  PubMed  CAS  Google Scholar 

  29. Yoshimoto T, Furukawa M, Yamamoto S, Horie T, Watanabe-Kohno S. Flavonoids: potent inhibitors of arachidonate 5-lipoxygenase. Biochem. Biophys. Res. Commun. 1983; 116: 612–618.

    Article  PubMed  CAS  Google Scholar 

  30. Alcaraz MJ, Hoult JRS. Actions of flavonoids and the novel anti-inflammatory flavone, hypolaetin-8-glucoside, on prostaglandin biosynthesis and inactivation. Biochem. Pharmacol. 1985; 34: 2477–2482.

    Article  PubMed  CAS  Google Scholar 

  31. Chang TH, Lee YC, Lee KY, Sun CH, Chang YP. Cocarcinogenic action of aspirin on gastric tumors induced byN-nitroso-N-methylnitroguanidine in rats. J. Natl. Cancer Inst. 1983; 70: 1067–1075.

    PubMed  CAS  Google Scholar 

  32. Kort WJ, Hulsman LOM, van Schalkwijk WP, Weijma IM, Zondervan PE, Westbroek DL. Reductive effect of aspirin treatment on primary tumor growth and metastasis of implanted fibrosarcoma in rats. J. Natl. Cancer Inst. 1986; 76: 711–720.

    PubMed  CAS  Google Scholar 

  33. Reddy BS, Rao CV, Rivenson A, Kelloff G. Inhibitory effect of aspirin on azoxymethane-induced colon carcinogenesis in F334 rats. Carcinogenesis 1993; 14: 1493–1497.

    Article  PubMed  CAS  Google Scholar 

  34. de la Lastra CA, Martin MJ, Motilva V. Antiulcer and gastroprotective effects of quercetin: a gross and histologic study. Pharmacol. 1994; 48: 56–62.

    Article  Google Scholar 

  35. Mohn GR, van Zeeland AA. Quantitative comparative mutagenesis in bacteria, mammalian cells, and animal-mediated assays. A convenient way of estimating genotoxic activity in vivo? Mutat. Res. 1985; 150: 159–175.

    PubMed  CAS  Google Scholar 

  36. Ogawa S, Hirayama T, Nohara M, Tokuda M, Hirai K, Fukui S. The effect of quercetin on the mutagenicity of 2-acetylaminofluorene and benzo[alpha]pyrene in Salmonella typhimurium strains. Mutat. Res. 1985; 142: 103–107.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Preventive Medicine, Kyoto Prefectural University of Medicine, Kyoto

    Yoshizumi Matsukawa, Mitsunori Yoshida, Fumiko Sato-Nishimori & Toshiyuki Sakai

  2. Biochemistry, Kyoto Prefectural University of Medicine, Kyoto

    Hoyoku Nishino

  3. 2nd Department of Pathology, Kyoto Prefectural University of Medicine, Kyoto

    Kanade Katsura & Tetsurou Takamatsu

  4. 1st Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto

    Junichi Okuzumi

  5. Hyogo Institute for Oriental Medicine, Higashidaimotsu-cho, 660-0828, Hyogo, Japan

    Yoshizumi Matsukawa, Katsuhiko Matsumoto & Fumiko Sato-Nishimori

  6. Department of Pathology, Shiga University of Medical Science, Shiga

    Hiroyuki Sugihara

Authors
  1. Yoshizumi Matsukawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hoyoku Nishino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mitsunori Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hiroyuki Sugihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kanade Katsura
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tetsurou Takamatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Junichi Okuzumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Katsuhiko Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Fumiko Sato-Nishimori
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Toshiyuki Sakai
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This work was supported in part by a SRF Grant for Biomedical Research (T.S.).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Matsukawa, Y., Nishino, H., Yoshida, M. et al. Quercetin enhances tumorigenicity induced by N-ethyl-N′-nitro-N-nitrosoguanidine in the duodenum of mice. Environ Health Prev Med 6, 235–239 (2002). https://doi.org/10.1007/BF02897975

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02897975

Key words

Search

Navigation