Radiation-induced signal transduction. Mechanisms and consequences

Over a dose range up to 50 Gy of low-LET (linear energy transfer) ionizing radiation and up to 5 kJ/m(2) UVB, mammalian cells convert molecular damage into productive response (mostly gain of function). By inactivation of neg ative regulatory components, such as protein tyrosine phosphatases as one m echanism discovered, the balance between restraining and stimulating influe nces is disturbed and an Increase In signal flow results. Also DNA damage c ausing transcriptional arrest produces a signaling cascade of as yet unknow n details. Such stimulation of the intracellular communication network can lead to apoptosis, elevated cell cycling and differentiation processes poss ibly including repair and recombination. The outcome likely depends on inte gration of all signals received which is as yet ill-understood. Although ac curate determinations of low-dose inductions have not been achieved for tec hnical reasons, the dose-response curves of induced signal transduction lik ely show threshold characteristics, in contrast to the direct consequences of DNA damage. ((C) Academie des sciences / Elsevier, Paris.)