We investigated mutations of the Tp53 tumor suppressor gene (formerly known as p53) in the lung tumors induced in rats after inhalation of plutonium dioxide ((239)PuO(2)) aerosols. Exons 5, 6, 7 and 8 of the Tp53 gene were examined for mutations by single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction (PCR)-amplified fragments and direct sequencing analysis. Almost all the mutations were guanine (G) to adenine (A) transitions and were distributed in exons 5 and 6. The Tp53 mutations occurred in lung tumors of various phenotypes and levels of immunohistochemical staining of Tp53 nuclear protein. These results indicate that the Tp53 mutations are not associated with tumor phenotype and nuclear accumulation of Tp53 protein, and that the G to A transition could be a common point mutation in the lung tumors seen after the inhalation of plutonium dioxide. The point mutations in the Tp53 gene seem to play a role in the development of lung tumors in rats after inhalation exposures to plutonium dioxide.