title: From targets to genes: a brief history of radiosensitivity.
abstract: The biological work of Douglas Lea spanned the period from 1934 to his early death in 1947, and during this short period he made important contributions to the theory of radiation action. He interpreted experimental data relating to the effects of radiation on viruses, bacteria, bean roots, etc in terms of the inactivation of discrete targets, which he identified with cellular genes. He thus laid the foundation of much subsequent research. It is now well recognized that mammalian cells differ substantially in radiosensitivity, especially in the low-dose region of the survival curve. The dependence of radiosensitivity on dose rate has been widely studied; this has practical significance for clinical radiotherapy as well as mechanistic implications. Since Lea's time there have been a number of efforts to describe models that can relate cell killing to radiation dose, dose rate, and track structure. So far these have not led to a comprehensive and widely accepted picture. Microdosimetric considerations lead to the concept of differing severity of lesions induced in DNA. Much is known about the sequence of processes that subsequently lead to cell inactivation: this can be divided into phases of induction, processing, and manifestation. Chromosomal events are currently attracting much attention, as they did in Lea's time. Considerable progress has also been made in identifying genes that control the repair of radiation damage. It has been found that mutation is frequently associated with the loss of a large segment of the genome around the damage site and this will have important implications for interactive processes between particle tracks.
authors: Institute of Cancer Research, Sutton, Surrey, UK.
authors: G G
authors: GG
authors: Steel
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects*; D049673:History, 20th Century; D006801:Humans; D008322:Mammals; D011839:Radiation, Ionizing; D011853:Radiobiology / Q000266:history; D011878:Radiotherapy; D006113:United Kingdom