Development of primary tissue culture techniques for use in radiobiology.

Many of the underlying theories of radiation biology have been developed using a combination of in vitro assays and work with animals. The aim of this dual approach was to develop and test general models using simple methods with in vitro cell lines and then to validate the results by testing their applicability in whole animals. Conversely, observations in whole animals could be modeled using cell lines in the search for mechanisms. In theory this approach is sound, but in many instances easy-to-grow cell lines were chosen which bore little resemblance to any tissue, and validation of the data in animals, if attempted at all, was done in very inbred strains of mice which were therefore genetically homogeneous. This called into question the relevance of the data for addressing questions in radiotherapy and radiation carcinogenesis in humans. In recent years, the development of elegant in situ molecular biology methods and the advances in our understanding of complex tissue biology have led to the development of tissue culture methods which aim to simulate the in vivo characteristics of the intact organ while allowing experimentation in vitro. The aim of this paper is to discuss the use and the limitations of these techniques and models in radiobiology and to indicate where they have changed or are likely to change our views of normal-tissue radiobiology.