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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)
  • Published : 2014.09.15

Abstract

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.

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