Low susceptibility to N-ethyl-N-nitrosourea-induced transplacental carcinogenesis in Long-Evans Cinnamon (LEC) rats.
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 O(6)-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.
Tsuchigauchi
Takeshi
T
Department of Molecular and Environmental Pathology, the University of Tokushima Graduate School, Tokushima, Japan.
Takahashi
Tetsuyuki
T
Ohnishi
Takamasa
T
Ogawa
Hirohisa
H
Bando
Yoshimi
Y
Uehara
Hisanori
H
Takizawa
Tamotsu
T
Kaneda
Shinya
S
Nakai
Tokiko
T
Shiota
Hiroshi
H
Izumi
Keisuke
K
D000818:Animals; D001483:Base Sequence; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D005038:Ethylnitrosourea / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008175:Lung Neoplasms / Q000139:chemically induced; D008297:Male; D008431:Maternal-Fetal Exchange; D008668:Metallothionein / Q000235:genetics; D009423:Nervous System Neoplasms / Q000139:chemically induced; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D020332:Rats, Inbred LEC; D020318:Rats, Long-Evans; D013045:Species Specificity
D002273:Carcinogens; C491055:Mt2A protein, rat; D012333:RNA, Messenger; D008668:Metallothionein; D019853:O(6)-Methylguanine-DNA Methyltransferase; D005038:Ethylnitrosourea