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No Effect of High Fat Diet-Induced Obesity on Spontaneous Reporter Gene Mutations in gpt Delta Mice

  • Takasu, Shinji (Division of Pathology, National Institute of Health Sciences) ;
  • Ishii, Yuji (Division of Pathology, National Institute of Health Sciences) ;
  • Matsushita, Kohei (Division of Pathology, National Institute of Health Sciences) ;
  • Kuroda, Ken (Division of Pathology, National Institute of Health Sciences) ;
  • Kijima, Aki (Division of Pathology, National Institute of Health Sciences) ;
  • Kodama, Yukio (Division of Toxicology, National Institute of Health Sciences) ;
  • Ogawa, Kumiko (Division of Pathology, National Institute of Health Sciences) ;
  • Umemura, Takashi (Division of Pathology, National Institute of Health Sciences)
  • 발행 : 2014.09.15

초록

A large number of epidemiological studies have demonstrated that obesity is a risk factor for several human cancers. Several animal studies using rodents with diet-induced or genetic obesity have also demonstrated that obesity can promote tumor development. However, the effects of obesity on the early stages of carcinogenesis, and especially on the spontaneous occurrence of somatic gene mutations, remain unclear. To investigate the effects of obesity on the rate of spontaneous gene mutations, we performed reporter gene mutation assays in liver, kidney, and colon, organs in which obesity appears to be associated with cancer development on the basis of epidemiological or animal studies, in mice with high fat diet (HFD)-induced obesity. Six-week-old male and female C57BL/6 gpt delta mice were fed HFD or standard diet (STD) for 13 or 26 weeks. At the end of the experiments, reporter gene mutation assays of liver, kidney, and colon were performed. Final body weights and serum leptin levels of male and female mice fed HFD for 13 or 26 weeks were significantly increased compared with corresponding STD-fed groups. Reporter gene mutation assays of liver, kidney, and colon revealed that there were no significant differences in gpt or $Spi^-$ mutant frequencies between STD- and HFD-fed mice in either the 13-week or 26-week groups. These results indicate that HFD treatment and consequent obesity does not appear to influence the spontaneous occurrence of somatic gene mutations.

키워드

참고문헌

  1. Aoki Y, Hashimoto AH, Amanuma K, et al (2007). Enhanced spontaneous and benzo(a)pyrene-induced mutations in the lung of Nrf2-deficient gpt delta mice. Cancer Res, 67, 5643-8. https://doi.org/10.1158/0008-5472.CAN-06-3355
  2. Bjorbaek C, Kahn BB (2004). Leptin signaling in the central nervous system and the periphery. Recent Prog Horm Res, 59, 305-31. https://doi.org/10.1210/rp.59.1.305
  3. Ceddia RB (2005). Direct metabolic regulation in skeletal muscle and fat tissue by leptin: implications for glucose and fatty acids homeostasis. Int J Obes (Lond), 29, 1175-83. https://doi.org/10.1038/sj.ijo.0803025
  4. Hirose Y, Hata K, Kuno T, et al (2004). Enhancement of development of azoxymethane-induced colonic premalignant lesions in C57BL/KsJ-db/db mice. Carcinogenesis, 25, 821-5.
  5. Iwasa J, Shimizu M, Shiraki M, et al (2010). Dietary supplementation with branched-chain amino acids suppresses diethylnitrosamine-induced liver tumorigenesis in obese and diabetic C57BL/KsJ-db/db mice. Cancer Sci, 101, 460-7. https://doi.org/10.1111/j.1349-7006.2009.01402.x
  6. Lee GH, Proenca R, Montez JM, et al (1996). Abnormal splicing of the leptin receptor in diabetic mice. Nature, 379, 632-5. https://doi.org/10.1038/379632a0
  7. Masumura K, Sakamoto Y, Ikeda M, et al (2011). Antigenotoxic effects of p53 on spontaneous and ultraviolet light B--induced deletions in the epidermis of gpt delta transgenic mice. Environ Mol Mutagen, 52, 244-52. https://doi.org/10.1002/em.20610
  8. Morrison DS, Parr CL, Lam TH, et al (2013). Behavioural and metabolic risk factors for mortality from colon and rectum cancer: analysis of data from the Asia-Pacific Cohort Studies Collaboration. Asian Pac J Cancer Prev, 14, 1083-7. https://doi.org/10.7314/APJCP.2013.14.2.1083
  9. Nohmi T, Suzuki T, and K. Masumura K (2000). Recent advances in the protocols of transgenic mouse mutation assays. Mutat Res, 455, 191-215. https://doi.org/10.1016/S0027-5107(00)00077-4
  10. Okamura T, Ishii Y, Suzuki Y, et al (2010). Effects of co-treatment of dextran sulfate sodium and MeIQx on genotoxicity and possible carcinogenicity in the colon of p53-deficient mice. J Toxicol Sci, 35, 731-41. https://doi.org/10.2131/jts.35.731
  11. Padidar S, Farquharson AJ, Williams LM, et al (2012). High-fat diet alters gene expression in the liver and colon: links to increased development of aberrant crypt foci. Dig Dis Sci, 57, 1866-74. https://doi.org/10.1007/s10620-012-2092-9
  12. Reddy BS, Maeura Y (1984). Tumor promotion by dietary fat in azoxymethane induced colon carcinogenesis in female F344 rats: influence of amount and sources of dietary fat. J Natl Cancer Inst, 72, 745-50.
  13. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M (2008). Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet, 371, 569-78. https://doi.org/10.1016/S0140-6736(08)60269-X
  14. Shimizu M, Sakai H, Shirakami Y, et al (2011). Preventive effects of (-)-epigallocatechin gallate on diethylnitrosamine-induced liver tumorigenesis in obese and diabetic C57BL/KsJ-db/db Mice. Cancer Prev Res, 4, 396-403. https://doi.org/10.1158/1940-6207.CAPR-10-0331
  15. Trak-Smayra V, Paradis V, Massart J, et al (2011). Pathology of the liver in obese and diabetic ob/ob and db/db mice fed a standard or high-calorie diet. Int J Exp Pathol, 92, 413-21. https://doi.org/10.1111/j.1365-2613.2011.00793.x
  16. van Kruijsdijk RC, van der Wall E, Visseren FL (2009). Obesity and Cancer: The role of dysfunctional adipose tissue. Cancer Epidemiol Biomarkers Prev, 18, 2569-78. https://doi.org/10.1158/1055-9965.EPI-09-0372
  17. Vansaun MN (2013). Molecular pathways: adiponectin and leptin signaling in cancer. Clin Cancer Res, 19, 1926-32. https://doi.org/10.1158/1078-0432.CCR-12-0930
  18. World Cancer Research Fund, / American Institute for Cancer Research (2007). Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective. Washington DC: AICR.

피인용 문헌

  1. Past, Present and Future Directions of gpt delta Rodent Gene Mutation Assays vol.4, pp.1, 2016, https://doi.org/10.14252/foodsafetyfscj.2015024