Reduction of p53 dosage renders mice hypersensitive to 7, 12-dimethylbenz(alpha) anthracene-induced salivary gland tumorigenesis.
BACKGROUND
The role of p53 during the evolutionary steps of experimental salivary gland tumorigenesis has not been fully elucidated.


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.


CONCLUSIONS
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.
Ide
Fumio
F
Department of Oral Pathology, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, Japan. idef@dent.meikai.ac.jp
Kitada
Munenori
M
Sakashita
Hideaki
H
Kusama
Kaoru
K
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000483:Alleles; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D003043:Cocarcinogenesis; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013365:Submandibular Gland Neoplasms / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000172:deficiency*
D002273:Carcinogens; D016159:Tumor Suppressor Protein p53; D015127:9,10-Dimethyl-1,2-benzanthracene