Hierarchical and cybernetic nature of biologic systems and their relevance to homeostatic adaptation to low-level exposures to oxidative stress-inducing agents.

Abstract

During evolution in an aerobic environment, multicellular organisms survived by adaptive responses to both the endogenous oxidative metabolism in the cells of the organism and the chemicals and low-level radiation to which they had been exposed. The defense repertoire exists at all levels of the biological hierarchy-from the molecular and biochemical level to the cellular and tissue level to the organ and organ system level. Cells contain preventive antioxidants to suppress oxidative damage to membranes. Cells also contain proteins and DNA; built-in redundancies for damaged molecules and organelles; tightly coupled redox systems; pools of reductants; antioxidants; DNA repair mechanisms and sensitive sensor molecules such as nuclear factor kappa beta; and signal transduction mechanisms affecting both transcription and post-translational 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 triggered by oxidative stress-induced signal transduction mechanisms-an epigenetic, not genotoxic, process. If the end points of cell proliferation, differentiation, or cell death are not seen at frequencies above background 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 proliferation and adaptive functions in a multicellular organism could provide protection of any one cell receiving deposited energy by the radiation tract through the sharing of reductants and by triggering apoptosis of target stem cells. Examples of the role of gap junctional intercellular communication in the adaptive response of cells and the bystander effect illustrate how the interaction of cells can modulate the effect of radiation on the single cell.

Study of the effect of refinery waste water exposure onAllium cepa's enzymatic antioxidant defense: probing potential biomarkers

“…Studies on the effect of Cd þþ on DNA damage in the liver of silver crucian carp (Carasscius auratus gibelio) indicated a sharp rise with an increase in Cd concentration (Cheng et al 2008). Moreover, repair of DNA strand breaks in moderately damaged cells, probably acts to protect organisms from further adverse effects of oxidative stress in the natural environment (Trosko 1998). This study also confirms the involvement of oxidative stress in A. cepa system generated by MRWW exposure.…”

Checking the Foundation: Recent Radiobiology and the Linear No-Threshold Theory

“…Rather, biological defenses against low doses appear to be dominated by epigenetic factors including hyperradiosensitivity (Joiner et al 1996;Skov 1999;Zeng et al 2006), bystander effects (Brooks 2004;Mothersill and Seymour 2004b;Prise et al 2003;Snyder 2004), adaptive responses (Day et al 2007a, b, c;Mitchel et al 1997;Mothersill and Seymour 2004a), induced genomic instability (Morgan 2003a) [though the significance of this phenomenon in normal cells (Dugan and Bedford 2003) and in vivo (Morgan 2003b) is uncertain], and interactions between the target cell and the extra-cellular matrix Barcellos-Hoff 2005;Barcellos-Hoff and Costes 2006). Rather than each cell functioning independently, multi-cellular organisms mount coordinated tissue-level responses to radiationinduced injury (Barcellos-Hoff and Brooks 2001;Feinendegen et al 2007;Trosko 1998). None of these phenomena occur in a linearly proportional relationship with dose in target cells.…”

“…Biological systems are organized hierarchically (Feinendegen et al 2007;Trosko 1998). Ionizing radiation acts at the atomic level, and effects may (or may not be) propagated up through the hierarchy to molecules (e.g., DNA), cells, tissues, and organisms.…”

Reasons to reconsider the significance of apoptosis for cancer therapy

“…With regard to the nucleus as the main important target of ionizing radiation, other authors propose a singlehit mechanism of tumour cell killing with the compacted chromatin probably representing a radiation-hypersensitive target (Chapman 2003). In contrast, other authors have focussed on the responses of plasma membranes to ionizing radiation and point in particular to the importance of cell-to-cell contacts through junctions, and the signalling mechanism through receptors (Ojeda et al 1994, Saran et al 1998, Trosko 1998, Koteles and Somosy 2001.…”