title: Medium-term multi-organ carcinogenesis bioassay of ethyl tertiary-butyl ether in rats.
abstract: The modifying potential of ethyl tertiary-butyl ether (ETBE) on tumor development was investigated in a medium-term multi-organ carcinogenesis bioassay using male F344 rats. Animals were sequentially given 5 carcinogens with different target sites in the first 4 weeks for multi-organ initiation. After one week they received ETBE by gavage at dose levels of 0 (control), 300 or 1000mg/kg/day until experimental week 28. Further groups were also given ETBE at doses of 0 or 1000mg/kg/day without prior carcinogen application. Incidences and multiplicities of follicular cell hyperplasias and neoplasms in the thyroid were significantly increased at dose levels of more than 300mg/kg/day. Combined incidences of squamous cell hyperplasias and papillomas of the forestomach were also significantly increased at 300 and 1000mg/kg/day. Incidences and multiplicities of adenocarcinomas in the colon were increased at 1000mg/kg/day. The numbers and areas of glutathione S-transferase placental form (GST-P) positive foci per unit area of the liver sections, and the incidence of hepatocellular adenomas were also significantly increased at 1000mg/kg/day, along with multiplicities of atypical hyperplasias of renal tubules of the kidney and the incidence of papillomatosis of the urinary bladder. This latter lesion was also seen at low incidence at 1000mg/kg/day without initiation. Thus, the current results indicate that ETBE has tumor promoting potential for the thyroid and forestomach at dose levels of 300mg/kg/day and more, and for the colon, liver, kidney and urinary bladder at 1000mg/kg/day, under the present experimental conditions.
authors.affiliation: DIMS Institute of Medical Science, Inc., Ichinomiya, Aichi, Japan. hagiwara@dims.co.jp
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hagiwara
authors.forename: Yuko
authors.initials: Y
authors.lastname: Doi
authors.forename: Norio
authors.initials: N
authors.lastname: Imai
authors.forename: Hironao
authors.initials: H
authors.lastname: Nakashima
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ono
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kawabe
authors.forename: Fumio
authors.initials: F
authors.lastname: Furukawa
authors.forename: Seiko
authors.initials: S
authors.lastname: Tamano
authors.forename: Kasuke
authors.initials: K
authors.lastname: Nagano
authors.forename: Shoji
authors.initials: S
authors.lastname: Fukushima
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology; D018248:Adenoma, Liver Cell / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D003043:Cocarcinogenesis; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology; D005019:Ethyl Ethers / Q000633:toxicity*; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D013964:Thyroid Neoplasms / Q000139:chemically induced / Q000473:pathology
chemical_list: D002273:Carcinogens; D005019:Ethyl Ethers; C098546:ethyl tert-butyl ether