The Frequency and Types of Spontaneous Mutations Found in the hprt and lacI Genes of Lymphocytes from Transgenic Big Blue Rats

In vivo assays are used to evaluate whether chemicals have the potential to induce genetic damage (mutations). In order to understand an assay and to use it for hazard identification, one must first understand the frequency and types of mutations that occur spontaneously (without any chemical exposure). This project is designed to evaluate spontaneous mutation in one gene that is in its normal location (Hprt) and one gene (lacI) that has been genetically engineered into a strain of rats. This strain of rats, containing the lacI transgene is called the Transgenic Big Blue Rat. The specific goals of this project are:
1) To determine the frequency of spontaneous mutation at the hprt and lacI loci in pre-weanling, young (four-month-old) and old (18-month-old) Big Blue rats.
2) To determine the types of mutations present in the mutants.
3) To determine if rats fed different diets have different spontaneous mutant
frequencies and if the types of mutations are different.
FY 2000 Accomplishments:
1) Continued sequencing mutants from mice fed different diets - NIH31 and AIN93 ad libitum and calorie restricted.
2) Presented poster at the Environmental Mutagen Society meeting and the FDA Science Symposium.
3) Invited presentation at Antimutagenesis Conference, Grand Rapids, Michigan.
4) Two invited seminars at the University of Arkansas at Pine Bluff (UAPB) and the Arkansas's Hospital, Little Rock, Arkansas.
FY 2001 Plans:
1) Finish analysis of point mutations in existing mutants.
2) Measure mutant frequencies in CD-1 weanlings and analyze mutations.
3) Prepare manuscripts for publication and submit technical report.