Carcinogenic alterations in murine liver, lung, and uterine tumors induced by in utero exposure to ionizing radiation

Katalin Lumniczky, Sára Antal, Emil Unger, Livius Wunderlich, Egon J. Hidvégi, Géza Sáfrány

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17 Citations (Scopus)

Abstract

The atomic bombing of Hiroshima and Nagasaki and the nuclear accident at Chernobyl raised the question of prenatal sensitivity to ionizing radiation- induced cancer. In this study, mice were exposed to single dose of Υ- radiation (0.2-2.0 Gy) at different embryonic stages. The tumor incidence increased with dose from 15 in control mice to 35% in mice irradiated with 2.0 Gy on 18 d of prenatal life. Various oncogenic events were investigated in lymphoid, liver, lung, and uterine tumors. We observed threefold to fivefold increases in myc expression in 25% of the lymphomas, and the expression of Ha-ras and p53 genes decreased in 40% and 60% of the lung tumors by twofold to fivefold. Point mutations were tissue specific: Ha-ras codon 61 mutations were found in about 40% of the liver adenocarcinomas, Ki- ras codon 12 mutations in about 17% of lung tumors, and p53 mutations in about 15% of the lymphomas. Amplification and rearrangement of the p53, myc, and Ha-, Ki- and N-ras genes were not detected. Loss of heterozygosity on chromosome 4 at the multiple tumor suppressor 1 and 2 genes was observed in all types of malignancies. Allelic losses on chromosome 11 at the p53 locus were found in lymphoid, liver, and lung tumors, but they were absent from uterine tumors. Multiple oncogenic changes were often detected. The frequency of carcinogenic alterations was similar in spontaneous and radiation-induced lymphoid, liver, and uterine tumors. In radiation-induced lung adenocarcinomas, however, the incidences of many oncogenic changes were different from those found in their spontaneous counterparts. This suggests that different oncogenic pathways are activated during spontaneous and in utero Υ-radiation-induced murine lung carcinogenesis.

Original languageEnglish
Pages (from-to)100-110
Number of pages11
JournalMolecular Carcinogenesis
Volume21
Issue number2
DOIs
Publication statusPublished - Mar 31 1998

Keywords

  • Loss of heterozygosity
  • Multiple tumor suppressor
  • Myc
  • Ras
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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