Radon and lung carcinogenesis: Mutability of p53 codons 249 and 250 to super(238)Pu alpha -particles in human bronchial epithelial cells

• Published in: Carcinogenesis (New York) 1997-01, Vol.18 (1), p.121-125
• Main Authors: Hussain, S P, Kennedy, CH, Amstad, P, Lui, H, Lechner, J F, Harris, C C
• Format: Article
• Language: English
• ISSN: 0143-3334

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 AGG super(arg) arrow right ATG super(met) 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 similar to 1460 working level months in uranium mining) of high LET alpha -radiation induced codon 249 AGG arrow right AAG transitions and codon 250 CCC arrow right ACC transversions with absolute mutation frequencies of 3.6 X 10 super(-7) and 3.8 X 10 super(-7) respectively. This mutation spectrum is consistent with our previous report of radon-associated human lung cancer.