TRANSFORMATION AND MUTAGENESIS

In vitro assays for transformation and mutagenesis represent powerful research tools. Because of the exquisite sensitivity of the experimental systems, possible in large self-contained experiments, low doses of radiation and/or chemicals can be studied that would be quite impractical to detect in human epidemiological surveys, or indeed in most experimental animal systems. The effects of doses of the order of cGy of neutrons or tens of cGy of gamma-rays can be detected and measured. The specific aims of this project fall into four categories. The first, using short-term in vitro cultures of Syrian hamster embryo (SHE) cells involves pragmatic aims of basic importance in radiation protection. We will investigate the inverse dose-rate effect, up to now demonstrated unequivocally only for C3H10 T1/2 cells. It is important to know if this effect is a general phenomenon or confined to one cell line. The in vitro assay will be used to investigate fractionated versus single doses of charged particles of defined LET, while the in utero/in vitro assay will be used for fractionation studies with 6 MeV neutrons. It is also planned to synchronize SHE cells in order to investigate the age response function for the transformational end-point. Second, SHE and C3H 10T1/2 cells will be used to assess the oncogenic potential of photoneutrons. Third, mutations in human keratinocytes and oncogenic transformation in SHE cells will be studied as a function of LET for charged particles in the track segment mode. These data will be fed into the core project entitled hierarchy of radiation effects which attempts to model the biological effects of radiation from patterns of energy deposition to the expression of biological effect. Fourth, we will continue to develop quantitative assays for transformation based on cells of human origin, and estimate the frequency with which radiation induces immortality and transformation. None exist at the present time that are truly quantitative. The goals of this project, therefore, are central to the principal mission of this program project, which is to investigate the biological effects of low doses of radiation.