N-ethyl-N-hydroxyethylnitrosamine (EHEN)-induced renal and hepatocarcinogenesis in the tumor suppressor Tsc2 transgenic rat.

Cancer Lett

Department of Experimental Pathology, Cancer Institute, Japanese Foundation for Cancer Research, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455, Japan.

Published: October 2002

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/s0304-3835(02)00209-4DOI Listing

Publication Analysis

Top Keywords

ehen-induced renal
8
renal hepatocarcinogenesis
8
tsc2 gene
8
tsc2
5
n-ethyl-n-hydroxyethylnitrosamine ehen-induced
4
renal
4
hepatocarcinogenesis tumor
4
tumor suppressor
4
suppressor tsc2
4
tsc2 transgenic
4

Similar Publications

Promotion of liver and kidney carcinogenesis by ethyl tertiary-butyl ether (ETBE) in male Wistar rats.

J Toxicol Pathol

October 2015

Japan Bioassay Research Center, Japan Industrial Safety and Health Association, 2445 Hirasawa, Hadano, Kanagawa 257-0015, Japan.

Tumor-promoting effects of ethyl tertiary-butyl ether (ETBE) were investigated in a 2-stage carcinogenesis bioassay with regard to hepatic and renal carcinogenesis in rats. Male 6-week-old Wistar rats were given drinking water containing N-ethyl-N-(2-hydroxyethyl)nitrosamine (EHEN), as an initiator, at a dose of 500 ppm for 2 weeks. Starting one week thereafter, the animals were administered ETBE at dose levels of 0 (control), 100, 300, 500 or 1,000 mg/kg/day by gavage for 19 weeks from week 4 to 22.

View Article and Find Full Text PDF

N-ethyl-N-hydroxyethylnitrosamine (EHEN)-induced renal and hepatocarcinogenesis in the tumor suppressor Tsc2 transgenic rat.

Cancer Lett

October 2002

Department of Experimental Pathology, Cancer Institute, Japanese Foundation for Cancer Research, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455, Japan.

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.

View Article and Find Full Text PDF

To characterize genetic alterations occurring in renal tumorigenesis, EHEN-induced renal cell tumors were examined using restriction landmark genomic scanning (RLGS) analysis, an electrophoretic separation technique that detects gene amplifications and deletions. Comparison of DNAs from tumor against those from corresponding nontumorous kidney and/or EHEN-treated kidney without development of renal tumors yielded specific alterations in terms of both amplified and reduced DNA spots. Two amplified spots were detected only in renal cell tumors and an additional four spots were frequent in EHEN-treated kidneys.

View Article and Find Full Text PDF

The modifying effects of concurrent administration of fish meal and sodium nitrite on the development of renal tumors after initiation with N-ethyl-N-hydroxyethylnitrosamine (EHEN) were investigated. A total of 120 male 6-week-old Wistar rats were divided into six groups. Groups 1-3 (30 animals each) were given 1000 ppm EHEN in their drinking water for 3 weeks as an initiation treatment for renal cancer induction and thereafter fed respective diets containing 64, 32, and 8% (original concentration in the basal diet) fish meal, and simultaneously given 0.

View Article and Find Full Text PDF

A number of cancer genes have been identified by the study of hereditary human cancers and shown to be involved in sporadic genesis of the same tumors. We have identified a germline mutation in the rat homologue of the human tuberous sclerosis (TSC2) predisposing gene in the Eker rat model. In this study, we searched for mutations of the Tsc2 gene in chemically induced non-Eker rat renal cell carcinomas (RCs).

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!