Transformation of human epidermal keratinocytes with fission neutrons

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Abstract
The biological effects of exposures to high LET radiations have particular relevance to radiation protection and risk assessment Since most cancers are of epithelial origin, it is important to obtain a better understanding of radiationinduced oncogenic transformation in this cell type. Accordingly we have initiated studies to determine whether immortalized human epidermal keratinocytes (RHEK) can be transformed with high LET radiations. Exponentially growing RHEK cells were treated with single doses (1, 10, 25, 50 and 100 cGy) of 0.85 MeV fission neutrons from the Janus reactor. Neutron exposure led to the development of morphologically altered cells and foci formation after 6 weeks at confluence. These transformed cultures grew with an increased saturation density, exhibited anchorageindependent growth and formed tumors hi athymlc mice. Single-strand conformatlonal polymorphism analysis and DNA sequencing demonstrated the absence of point mutations in codons 12/13 and 61 in the Ha-ras, Ki-ras, or N-ras genes and exons 4–9 of the pS3 tumor suppressor gene. These studies demonstrate that high LET radiations (fission neutrons) can transform immortalized human epithelial cells to a malignant phenotype that does notappear to involve mutations in either the cellular p53 or ras genes.

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