Low susceptibility to N-ethyl-N-nitrosourea-induced transplacental carcinogenesis in Long-Evans Cinnamon (LEC) rats

Takeshi Tsuchigauchi; Tetsuyuki Takahashi; Takamasa Ohnishi; Hirohisa Ogawa; Yoshimi Bando; Hisanori Uehara; Tamotsu Takizawa; Shinya Kaneda; Tokiko Nakai; Hiroshi Shiota; Keisuke Izumi

doi:10.2152/jmi.56.93

Originals

Low susceptibility to N-ethyl-N-nitrosourea-induced transplacental carcinogenesis in Long-Evans Cinnamon (LEC) rats

Takeshi Tsuchigauchi, Tetsuyuki Takahashi, Takamasa Ohnishi, Hirohisa Ogawa, Yoshimi Bando, Hisanori Uehara, Tamotsu Takizawa, Shinya Kaneda, Tokiko Nakai, Hiroshi Shiota, Keisuke Izumi

Author information

Takeshi Tsuchigauchi
Department of Molecular and Environmental Pathology, the University of Tokushima Graduate School
Department of Ophthalmology and Visual Neuroscience, Institute of Health Biosciences, the University of Tokushima Graduate School
Tetsuyuki Takahashi
Department of Molecular and Environmental Pathology, the University of Tokushima Graduate School
Takamasa Ohnishi
Department of Molecular and Environmental Pathology, the University of Tokushima Graduate School
Hirohisa Ogawa
Department of Molecular and Environmental Pathology, the University of Tokushima Graduate School
Yoshimi Bando
Department of Molecular and Environmental Pathology, the University of Tokushima Graduate School
Hisanori Uehara
Department of Molecular and Environmental Pathology, the University of Tokushima Graduate School
Tamotsu Takizawa
Department of Molecular and Environmental Pathology, the University of Tokushima Graduate School
Shinya Kaneda
Department of Molecular and Environmental Pathology, the University of Tokushima Graduate School
Tokiko Nakai
Department of Molecular and Environmental Pathology, the University of Tokushima Graduate School
Hiroshi Shiota
Department of Ophthalmology and Visual Neuroscience, Institute of Health Biosciences, the University of Tokushima Graduate School
Keisuke Izumi
Department of Molecular and Environmental Pathology, the University of Tokushima Graduate School

Keywords: Long-Evans Cinnamon rat, Long-Evans Agouti rat, N-ethyl-N-nitrosourea, trigeminal schwannoma, metallothionein, O⁶-methylduanine-DNA methyltransferase

JOURNAL FREE ACCESS

2009 Volume 56 Issue 3,4 Pages 93-98

DOI https://doi.org/10.2152/jmi.56.93

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Abstract

The Long-Evans Cinnamon (LEC) rat, an animal model of Wilson’s disease, is resistant to a variety of chemical carcinogenesis except liver and colon. In the present study, N-ethyl-N-nitrosourea (ENU)-induced transplacental carcinogenesis was examined in male and female LEC, Long-Evans Agouti (LEA), a sibling line of the LEC rat, and F344 rats (n=21). ENU was administered to pregnant rats as a single s.c. injection at a dose of 60 mg/kg body weight on the 17th day after conception. Cerebral/spinal gliomas and trigeminal/spinal nerve schwannomas developed in both LEA and F344 rats at 30 weeks of age, but no nervous system tumors developed in LEC rats, the difference being statistically significant. Lung adenomas also developed in LEA and F344 rats, but not in LEC rats. Semiquantitative RT-PCR demonstrated that metallothionein (MT)1a, MT2 and O⁶-methylguanine-DNA methyltransferase (MGMT) mRNA levels in the liver of LEC rats were higher than those in F344 and LEA rats. In addition, Western blot analysis showed that MT (MT1 plus MT2) in the liver of LEC rats was also higher than that in other strains. Present results suggest that high levels of MT and/or MGMT contribute to the resistance to nitrosamine-induced carcinogenesis in LEC rats. J. Med. Invest. 56: 93-98, August, 2009

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