title: Loss of p53 is an early event in induction of brain tumors in mice by transplacental carcinogen exposure.
abstract: Experimental carcinogenesis studies using p53-deficient mice have suggested that loss of function of this tumor suppressor gene is generally not an early event but is rather related to tumor progression. However, the biological functions of p53 and the accumulating evidence of alteration in human tumors imply a possible role for loss of p53 in the initial stages of tumorigenesis. Ethylnitrosourea administration to p53-heterozygous pregnant mice resulted in rapid development of primary brain tumors, which are extremely rare in mice, in 70% of the p53-null offspring. Brain tumors also developed later in 4% of heterozygous mice, but they had lost the wild-type allele. Thus, loss of normal p53 gene expression is of direct significance to early events in brain tumorigenesis, and this tumor suppressor gene may protect embryos from DNA damage in the brain induced by transplacental carcinogen exposure.
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Oda
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.forename: N
authors.initials: N
authors.lastname: Tsurutani
authors.forename: S
authors.initials: S
authors.lastname: Shimizu
authors.forename: Y
authors.initials: Y
authors.lastname: Nakatsuru
authors.forename: S
authors.initials: S
authors.lastname: Aizawa
authors.forename: T
authors.initials: T
authors.lastname: Ishikawa
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000139:chemically induced* / Q000235:genetics*; D002273:Carcinogens / Q000378:metabolism; D005038:Ethylnitrosourea / Q000378:metabolism; D005260:Female; D005333:Fetus; D017353:Gene Deletion; D016158:Genes, p53; D006801:Humans; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D008808:Mice, Inbred CBA / Q000235:genetics; D011247:Pregnancy
chemical_list: D002273:Carcinogens; D005038:Ethylnitrosourea