Molecular Analysis of Medaka Tumors: New Models for Carcinogenicity Testing
Abstract
The objective of this research is to develop the medaka as a model system to better understand the molecular mechanisms of chemical carcinogenesis. Although the medaka has been widely used in carcinogenicity studies for the past two decades, almost no information is available at the molecular level. We have focused our studies these past three years on the role of oncogenes and suppressor genes in tumorigenesis. We exposed medaka to three known carcinogens: diethylnitrosamine (DEN), methylaaoxymethanol acetate (MAMAc) and N-methyl-N' -nitro-N-nitrosoguanidine (MNNG). Animals exposed to either DEN or MAMAc developed liver tumors. Medaka exposed to MNNG, however, developed a wide array of extra- hepatic lesions. Our studies have shown that DNAs from these chemically-induced tumors are able to transform NIH3T3 cells and induce tumors in nude mice. One animal with a DEN- induced cholangiocarcinoma appears to have a novel - activated oncogene. Preliminary evidence indicates that DNA from MAMAc-induced hepatocellular cholangiocarcinomas - may contain activated K-ras and/or inactivated p53 genes. More sensitive PCR-based techniques are being developed to analyze the DNA from the MNNG-induced tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 07, 1994
- Accession Number
- ADA294562
Entities
People
- Rebecca Van Beneden
Organizations
- Duke University Hospital