No Promoting Effect of Ethyl Tertiary-butyl Ether (ETBE)on Rat Urinary Bladder Carcinogenesis Initiated with N-Butyl-N-(4-hydroxybutyl)nitrosamine

Akihiro Hagiwara; Norio Imai; Yuko Doi; Mayuko Suguro; Mayumi Kawabe; Fumio Furukawa; Kasuke Nagano; Shoji Fukushima

doi:10.1293/tox.2013-0027

Original Articles

No Promoting Effect of Ethyl Tertiary-butyl Ether (ETBE)on Rat Urinary Bladder Carcinogenesis Initiated with N-Butyl-N-(4-hydroxybutyl)nitrosamine

Akihiro Hagiwara, Norio Imai, Yuko Doi, Mayuko Suguro, Mayumi Kawabe, Fumio Furukawa, Kasuke Nagano, Shoji Fukushima

Author information

Akihiro Hagiwara
DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan
Norio Imai
DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan
Yuko Doi
DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan
Mayuko Suguro
DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan
Mayumi Kawabe
DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan
Fumio Furukawa
DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan
Kasuke Nagano
Nagano Toxicologic-Pathology Consulting, 467-7 Ojiri, Hadano, Kanagawa 257-0011, Japan
Shoji Fukushima
Japan Bioassay Research Center, Japan Industrial Safety and Health Association, 2445 Hirasawa, Hadano, Kanagawa 257-0015, Japan

Keywords: ETBE, initiation/promotion, urinary bladder carcinogenesis, papillomatosis, soft stone, F344 rats

JOURNAL FREE ACCESS

2013 Volume 26 Issue 4 Pages 351-357

DOI https://doi.org/10.1293/tox.2013-0027

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Abstract

The effects of ethyl tertiary-butyl ether (ETBE) on two-stage urinary bladder carcinogenesis in male F344 rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were investigated at various dose levels with regard to possible promoting activity. Groups of 30 rats were given drinking water containing 500 ppm BBN, as an initiator, for 4 weeks and starting one week thereafter received ETBE by gavage (daily, 7 days/week) at dose levels of 0 (control), 100, 300, 500 or 1000 mg/kg/day until experimental week 36. No statistically significant differences in incidences of preneoplastic lesions, papillomas, and carcinomas of the urinary bladder were evident in rats treated with 100–1000 mg/kg/day ETBE as compared with control values. Furthermore, the average numbers of preneoplastic or neoplastic lesions per unit length of basement membrane in rats given 100–1000 mg/kg/day ETBE were also comparable to control values. However, papillomatosis of the urinary bladder was found in 4 out of 30 rats (13%) in the group given 1000 mg/kg/day ETBE, and soft stones in the urinary bladder were found in 3 out of these 4 rats. The results thus demonstrated that ETBE did not exert promotional activity on urinary bladder carcinogenesis. However, papillomatosis of the urinary bladder developed in small numbers of the rats given ETBE at 1000 mg/kg/day but not in rats given 500 mg/kg/day or lower doses.

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