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The Effect of P53 Null Phenotype on Bleomycin-Induced Stress Protein Elicitation In Vivo in Transgenic Mice


Investigate the structure of the stress protein (sp) 70 and 90 genes by Southern blot in the 8-10 week old p53 null mouse in comparison with C57BL/6 control mouse; 2. Investigate the stress protein metabolic turnover (synthesis 35S-labeling) as a reflection of gene expression in the control homozygous C57BL/6 (+/+) and the null p53 homozygous TSG (-/-) mice as elicited by bleomycin (BL) at 1, 2, 3, 4 and 5 mo. of age (during the G1-phase of the cell cycle) by polyacrylamide gel electrophoresis (PAGE), and their levels of radio-labeling calculated by computerized electronic area measurements. If stress proteins (sps) are absent in bone marrow nuclei of 1 month old p53 null mice (sp synthesis is dependent on the presence of the p53 gene) or if their expression is below the level of measurement then the protocol will be discontinued at test group 1, see below. 3. Investigate the phosphorylation patterns of sps as a reflection of gene expression as elicited by BL using the same animal types, time frames and techniques as in Objective 1. 4. Identify and examine nuclear polypeptides other than sps for synthesis and phosphorylation levels as possible biomarkers of metabolic alterations and gene expression during phases of the cell cycle in control and homozygous p53 null mice following administration of BL.

Manjanatha, Mugimane
DHHS/FDA - National Center for Toxicological Research
Project number