N-ethyl-N-hydroxyethylnitrosamine (EHEN)-induced renal and hepatocarcinogenesis in the tumor suppressor Tsc2 transgenic rat.
Hereditary renal carcinomas (RCs) develop in Tsc2 gene mutant (Eker) rats around the age of 1 year. We previously reported that Tsc2 mutations were detected in chemically (N-ethyl-N-hydroxyethylnitrosamine (EHEN) and diethylnitrosamine)-induced non-Eker rat RCs, suggesting an involvement of Tsc2 alteration in rat RC development. In this study, we evaluated the effect of extra copies of the Tsc2 gene on renal and hepatocarcinogenesis that was induced by EHEN in vivo. The incidence of RCs in non-transgenic rats (2/17) is slightly higher than in transgenic rats (0/32), although it is statistically not significant. These results suggest the presence of other target RC gene(s) in chemically (EHEN)-induced renal carcinogenesis. We observed no difference in the numbers and areas of the hepatic glutathione S-transferase placental type positive foci.
Department of Experimental Pathology, Cancer Institute, Japanese Foundation for Cancer Research, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455, Japan.
Nobuo
N
Satake
Makoto
M
Miyagawa
Junko
J
Sakurai
Hiroaki
H
Mitani
Toshiyuki
T
Kobayashi
Hiroshi
H
Tamura
Okio
O
Hino
D000818:Animals; D030801:Animals, Genetically Modified; D002273:Carcinogens / Q000633:toxicity; D004052:Diethylnitrosamine / Q000031:analogs & derivatives* / Q000633:toxicity*; D005260:Female; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D006801:Humans; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D008113:Liver Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012097:Repressor Proteins / Q000235:genetics*; D012727:Sex Characteristics; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
D002273:Carcinogens; D012097:Repressor Proteins; C000624653:TSC2 protein, human; C000624655:Tsc2 protein, rat; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C023845:N-ethyl-N-hydroxyethylnitrosamine; D004052:Diethylnitrosamine