title: Nivalenol, a main Fusarium toxin in dietary foods from high-risk areas of cancer of esophagus and gastric cardia in China, induced benign and malignant tumors in mice.
abstract: This is the first report that a Fusarium toxin nivalenol (NIV) naturally existing at high levels in dietary food in high-risk areas of cancer of esophagus and gastric cardia in China induced benign and malignant tumors in mice. The levels of two Fusarium toxins, nivalenol and deoxynivalenol (DON) were quantitated using high performance liquid chromatography (HPLC) in a total of 97 samples of dietary wheat flour, barley and corn collected from families in two areas with high mortality rate of cancer of esophagus and gastric cardia (132/100,000), Linxian, Henan province and Cixiang, Hepei province, China. The mean level of NIV and DON in three dietary foods was 830+/-927 microg/kg (range 584-1,780 microg/kg) and 4,281+/-6,114 microg/kg (range 732-10,980 microg/kg) respectively. The highest mean level of NIV was 1,780+/-1,705 microg/kg found in barley from Linxian, that of DON was 10,980+/-10,139 microg/kg found in corn from Cixiang. NIV was undetectable in 2 samples of rice from USA. The mean levels of NIV in three main dietary foods in those two high-risk areas were estimated at 400 to 800-fold higher than that in the USA, where NIV was undetectable in dietary food, and the mortality rate of esophageal cancer is <5/100,000 in white Caucasians in the USA, (odds ratio was estimated at 17-34, p<0.000005). These data suggest that Linxian and Cixiang peasants who consumed a diet with high NIV had significantly higher risk for developing esophageal cancer than the US residents who consumed food without or with negligible amounts of NIV. Three repeated experiments were performed using Balb/C mice with inter-mittent application of NIV, alternate with 12-Tetradeconoyl-phorbol-13-acetate (TPA) application on skin. Papillomas and carcinomas developed in a total of 23/49 (47%) mice that survived 11-60 weeks of experiments. Among all the tumors, 4 carcinomas in 3 mice were identified. No tumors were found in the 60 control mice applying either TPA or acetone (solvent) only on skin.
authors.affiliation: Laboratory of Hepatitis and Related Emerging Agents, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, FDA, Bethesda, MD, USA. hsia@cber.fda.gov
authors.forename: Chu Chieh
authors.initials: CC
authors.lastname: Hsia
authors.forename: Ze Yuan
authors.initials: ZY
authors.lastname: Wu
authors.forename: Yun Sian
authors.initials: YS
authors.lastname: Li
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Zong Tang
authors.initials: ZT
authors.lastname: Sun
mesh_terms: D000821:Animal Feed; D000818:Animals; D002277:Carcinoma; D002299:Cardia / Q000473:pathology*; D002851:Chromatography, High Pressure Liquid; D002869:Chromosome Aberrations; D004032:Diet; D004938:Esophageal Neoplasms / Q000139:chemically induced*; D005260:Female; D005433:Flour; D005670:Fusarium / Q000378:metabolism*; D001467:Hordeum / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009183:Mycotoxins / Q000737:chemistry; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D016017:Odds Ratio; D010212:Papilloma; D013274:Stomach Neoplasms / Q000139:chemically induced*; D013696:Temperature; D014255:Trichothecenes / Q000494:pharmacology*; D003313:Zea mays / Q000378:metabolism
chemical_list: D009183:Mycotoxins; D014255:Trichothecenes; C038405:nivalenol; C007262:deoxynivalenol