HIERARCHICAL AND CYBERNETIC NATURE OF BIOLOGIC SYSTEMS AND THEIR RELEVANCE TO HOMEOSTATIC ADAPTATION TO LOW-LEVEL EXPOSURES TO OXIDATIVE STRESS-INDUCING AGENTS

During evolution in an aerobic environment, multicellular organisms su rvived by adaptive responses to both the endogenous oxidative metaboli sm in the cells of the organism and the chemicals and low-level radiat ion to which they had been exposed. The defense repertoire exists at a ll levels of the biological hierarchy-from the molecular and biochemic al level to the cellular and tissue level to the organ and organ syste m level. Cells contain preventive antioxidants to suppress oxidative d amage to membranes. Cells also contain proteins and DNA; built-in redu ndancies for damaged molecules and organelles; tightly coupled redox s ystems; pools of reductants; antioxidants; DNA repair mechanisms and s ensitive sensor molecules such as nuclear factor kappa beta; and signa l transduction mechanisms affecting both transcription and post-transl ational modification of proteins needed to cope with oxidative stress. The biologic consequences of the low-level radiation that exceeds the background level of oxidative damage could be necrosis or apoptosis, cell proliferation, or cell differentiation. These effects are trigger ed by oxidative stress-induced signal transduction mechanisms-an epige netic, not genotoxic, process, if the end points of cell proliferation , differentiation, or cell death are not seen at frequencies above bac kground levels in an organism, it is unlikely that low-level radiation would play a role in the multistep processes of chronic diseases such as cancer. The mechanism linked to homeostatic regulation of prolifer ation and adaptive functions in a multicellular organism could provide protection of any one cell receiving deposited energy by the radiatio n tract through the sharing of reductants and by triggering apoptosis of target stem cells. Examples of the role of gap junctional intercell ular communication in the adaptive response of cells and the bystander effect illustrate how the interaction of cells can modulate the effec t of radiation on the single cell.