WHAT WILL MOLECULAR-BIOLOGY CONTRIBUTE TO OUR UNDERSTANDING OF RADIATION-INDUCED CELL-KILLING AND CARCINOGENESIS

The vast body of radiobiological data accumulated with mammalian syste ms in vitro and in vivo has had an enormous impact on radiotherapy. Ho wever, while quantitative, these data are essentially phenomenological , and it is only in the last decade or so that the techniques of molec ular biology allow basic mechanisms to be understood. This will be ill ustrated by two examples, one involving cell killing and the other car cinogenesis. The identification and sequencing of repair and checkpoin t control genes in the yeast S. pombe allow the mechanism of sensitivi ty/resistance to radiation to be understood at the molecular level. Th e development of techniques to identify mutations in mismatch repair g enes have made it possible to show that such mutations are associated with a wide range of human cancers and are a likely mechanism of radia tion induced malignancies. Tikvah Alper would have been delighted to s ee the central role that microorganisms have played in these recent de velopments.