Radon and lung carcinogenesis : mutability of p53 codons 249 and 250 to 238Pu α-particles in human bronchial epithelial cells

Radon-222, a decay product of uranium-238 and a source of high linear energy transfer (LET) alpha-particles, has been implicated in the increased risk of lung cancer in uranium miners as well as non-miners. p53 mutation spectrum studies of radon-associated lung cancer have failed to show any specifi...

Full description

Saved in:
Bibliographic Details
Published in:Carcinogenesis (New York) 1997, Vol.18 (1), p.121-125
Main Authors: HUSSAIN, S. P, KENNEDY, C. H, AMSTAD, P, LUI, H, LECHNER, J. F, HARRIS, C. C
Format: Article
Language:English
Subjects:
Adolescent
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Codon - genetics
Codon - radiation effects
Genes, p53 - genetics
Genes, p53 - radiation effects
Humans
Lung Neoplasms - genetics
Male
Medical sciences
Mutagenesis
Mutagenicity Tests
Neoplasms, Radiation-Induced - genetics
Physical agents
Radon - toxicity
Tumors
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Radon-222, a decay product of uranium-238 and a source of high linear energy transfer (LET) alpha-particles, has been implicated in the increased risk of lung cancer in uranium miners as well as non-miners. p53 mutation spectrum studies of radon-associated lung cancer have failed to show any specific mutational hot spot with the exception of a single study in which 31% of squamous cell and large cell lung cancers from uranium miners showed a p53 codon 249 AGGarg --> ATGmet mutation. Although the results of laboratory studies indicate that double-strand breaks and deletions are the principal genetic alterations caused by alpha-particles, uncertainty still prevails in the description of DNA damage in radon-associated human lung cancer. In the present study, we have evaluated the mutability of p53 codons 249 and 250 to alpha-particles in normal human bronchial epithelial (NHBE) cells using a highly sensitive genotypic mutation assay. Exposure of NHBE cells to a total dose of 4 Gy (equivalent to approximately 1460 working level months in uranium mining) of high LET alpha-radiation induced codon 249 AGG --> AAG transitions and codon 250 CCC --> ACC transversions with absolute mutation frequencies of 3.6 x 10(-7) and 3.8 x 10(-7) respectively. This mutation spectrum is consistent with our previous report of radon-associated human lung cancer.
ISSN:0143-3334
1460-2180
1460-2180
DOI:10.1093/carcin/18.1.121