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  • Title: Reduction of p53 dosage renders mice hypersensitive to 7, 12-dimethylbenz(alpha) anthracene-induced salivary gland tumorigenesis.
    Author: Ide F, Kitada M, Sakashita H, Kusama K.
    Journal: Anticancer Res; 2003; 23(1A):201-4. PubMed ID: 12680213.
    Abstract:
    BACKGROUND: The role of p53 during the evolutionary steps of experimental salivary gland tumorigenesis has not been fully elucidated. MATERIALS AND METHODS: Each genotype group of p53-deficient mice received a single intrasubmandibular gland injection of 1 mg of 7, 12-dimethylbenz(a)anthracene. In addition to the routine histopathological examination, immunohistochemical detection of p53 protein and molecular biological analysis of wild-type p53 allele status in the p53+/- tumors developed were performed. RESULTS: Fourteen weeks following injection, submandibular gland tumors developed in 100% of p53-/- and 70% of p53+/- mice, whereas only 10% of p53+/+ mice yielded tumors. Salivary gland tumors in p53-deficient mice were predominantly sarcomas (70%). In 64% of p53+/- tumors, overexpression of a mutant version of p53 protein was evident. Loss of the wild-type allele of p53 could not be detected in all p53+/- tumors. CONCLUSION: The earlier tumor development in p53-deficient mice provides the in vivo evidence that reduction of p53 dosage or possibly p53 haploinsufficiency might be sufficient to promote salivary gland tumorigenesis.
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