How Do Tissues Respond to Damage at the Cellular Level? The Role of Cytokines in Irradiated Tissues

TLDR

Ionizing radiation affects tissue function and tumor control largely through DNA damage, yet multicellular organisms depend on intercellular cooperation, making the complex interplay of cellular events crucial to understanding tissue responses. The study asks whether tissue response to ionizing radiation is merely the sum of individual cellular effects or whether tissues act as coherent units in response to cellular damage. The authors review evidence that cytokines, especially transforming growth factor beta1, serve as key extracellular signaling mediators of tissue response to radiation.

Abstract

The capacity of ionizing radiation to affect tissue function, control tumor growth and elicit pathological sequelae has been attributed in great part to its effects on cellular DNA, which, as the transmitter of genetic information, can both register damage and perpetuate it. Nonetheless, multicellular organisms function as the result of the cooperation of many cell types. What then occurs when individual cells are damaged by ionizing radiation? Is tissue response a sum of cellular effects such as cell death and DNA damage? Or does the tissue respond as a coherent unit to the damage of its parts? In this paper, data in support of the latter model that indicate a role for cytokines, in particular transforming growth factor beta1, as critical components of extracellular signaling pathways that mediate tissue response to radiation will be reviewed. The key to manipulating the consequences of radiation exposure lies in understanding the complex interplay of events initiated at the cellular level, but acting on the tissue.