title: Dietary fructose enhances the incidence of precancerous hepatocytes induced by administration of diethylnitrosamine in rat.
abstract: BACKGROUND
  Nonalcoholic fatty liver disease (NAFLD) is a risk for hepatocellular carcinoma (HCC), but the association between a high-fructose diet and HCC is not fully understood. In this study, we investigated whether a high-fructose diet affects hepatocarcinogenesis induced by administration of diethylnitrosamine (DEN).
  
  
  METHODS
  Seven-week-old male Sprague-Dawley rats were fed standard chow (controls), a high-fat diet (54% fat), or a high-fructose diet (66% fructose) for 8 weeks. All rats were given DEN at 50 μg/L in drinking water during the same period. Precancerous hepatocytes were detected by immunostaining of the placental form of glutathione-S-transferase (GST-P). The number of GST-P-positive hepatocytes was assessed in liver specimens.
  
  
  RESULTS
  Serum levels of total cholesterol were similar among the three groups, but serum triglyceride, fasting blood glucose, and insulin levels were higher in the high-fructose group compared to the high-fat group. In contrast, hepatic steatosis was more severe in the high-fat group compared with the high-fructose and control groups, but the incidence of GST-P-positive specimens was significantly higher in the high-fructose group compared to the other two groups. The average number of GST-P-positive hepatocytes in GST-P positive specimens in the high-fructose group was also higher than those in the other two groups. This high prevalence of GST-P-positive hepatocytes was accompanied by higher levels of 8-hydroxydeoxyguanosine in serum and liver tissue.
  
  
  CONCLUSIONS
  These results indicate that dietary fructose, rather than dietary fat, increases the incidence of precancerous hepatocytes induced by administration of DEN via insulin resistance and oxidative stress in rat. Thus, excessive fructose intake may be a potential risk factor for hepatocarcinogenesis.
authors: Ryo
authors: R
authors: Kumamoto
authors: Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, Kagoshima 890-8544, Japan. hirouto@m2.kufm.kagoshima-u.ac.jp.
authors: Hirofumi
authors: H
authors: Uto
authors: Kohei
authors: K
authors: Oda
authors: Rie
authors: R
authors: Ibusuki
authors: Shirou
authors: S
authors: Tanoue
authors: Shiho
authors: S
authors: Arima
authors: Seiichi
authors: S
authors: Mawatari
authors: Kotaro
authors: K
authors: Kumagai
authors: Masatsugu
authors: M
authors: Numata
authors: Tsutomu
authors: T
authors: Tamai
authors: Akihiro
authors: A
authors: Moriuchi
authors: Hiroshi
authors: H
authors: Fujita
authors: Makoto
authors: M
authors: Oketani
authors: Akio
authors: A
authors: Ido
authors: Hirohito
authors: H
authors: Tsubouchi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D059305:Diet, High-Fat; D004040:Dietary Carbohydrates / Q000008:administration & dosage* / Q000494:pharmacology*; D004052:Diethylnitrosamine / Q000008:administration & dosage / Q000494:pharmacology; D005234:Fatty Liver / Q000097:blood / Q000201:enzymology / Q000473:pathology; D005632:Fructose / Q000008:administration & dosage* / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005982:Glutathione Transferase / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D015994:Incidence; D008297:Male; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D011230:Precancerous Conditions / Q000097:blood / Q000201:enzymology / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D004040:Dietary Carbohydrates; D012333:RNA, Messenger; D005632:Fructose; D004052:Diethylnitrosamine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005982:Glutathione Transferase; D003849:Deoxyguanosine