Comparative study on Tp53 gene mutations in lung tumors from rats exposed to 239Pu, 237Np and 222Rn.
The tumor suppressor gene Tp53 was analyzed by polymerase chain reaction-amplification of genomic DNA extracted from paraffin-embedded tissue sections of rat lung tumors to compare mutations that occurred after inhalation exposures to plutonium dioxide, neptunium dioxide, or radon and radon progenies. Exons 5 to 8 of the gene were amplified in 16 plutonium-, 23 neptunium- and 15 radon-induced lung tumors, and their polymerase chain reaction products were examined for mutations by single strand conformational polymorphism analysis and direct sequencing method. Two point mutations were detected in the plutonium-induced tumors, i.e., a guanine to adenine transition at codon 219 of exon 6 and a cytosine to thymine transition at codon 266 of exon 8. Although only one point mutation was found at codon 175 of exon 5 (cytosine to thymine transition) from neptunium-induced tumors, no mutations were detectable from radon-induced tumors. These results indicate that the abnormalities of the Tp53 gene might not be so critical for the pulmonary carcinogenesis after the inhalation of different alpha emitters, even though the presence and frequencies of the Tp53 gene mutations were different.
Yamada
Yutaka
Y
Internal Radiation Effects Research Group, National Institute of Radiological Sciences, Chiba, Japan. yt_yamada@nirs.go.jp
Oghiso
Yoichi
Y
Morlier
Jean-Paul
JP
Guillet
Kristell
K
Fritsch
Paul
P
Dudoignon
Nicolas
N
Monchaux
Georges
G
D000280:Administration, Inhalation; D000512:Alpha Particles / Q000009:adverse effects; D000818:Animals; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D016158:Genes, p53 / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D009405:Neptunium / Q000008:administration & dosage / Q000506:poisoning*; D011005:Plutonium / Q000008:administration & dosage / Q000506:poisoning*; D011829:Radiation Dosage; D011886:Radon / Q000008:administration & dosage* / Q000506:poisoning; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012062:Relative Biological Effectiveness; D013534:Survival; D016019:Survival Analysis
D004273:DNA, Neoplasm; D011005:Plutonium; D009405:Neptunium; D011886:Radon