Dose-Response: An International Journal: Volume 6, Issue 3
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2008-30-09
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Dose-Response, Vol 6, no 3, Table of Contents
(2008-09-01)
SUPEROXIDE DISMUTASE, LIPID PEROXIDATION, AND BELL-SHAPED DOSE RESPONSE CURVES
(2008-09-01) McCord, Joe M
Cellular metabolism generates the cytotoxic superoxide free radical, O2·–, and a family of enzymes called superoxide dismutases (SOD) protects us from O2·– by catalyzing its conversion to O2 and H2O2. Superoxide production increases in a wide variety of pathological states, especially those involving inflammation or ischemic injury. Most of the literature has described systems wherein added or over expressed SOD produced beneficial effects, yet in some circumstances SOD provided no benefit, or was clearly detrimental, exacerbating cell injury or death. When broad dose-response studies were finally possible in models of reperfusion injury in the isolated heart, hormesis became clear. We propose that the mechanisms underlying the hormesis are related to the paradoxical abilities of the superoxide radical to serve as both an initiator and a terminator of the free radicalmediated chain reaction that results in lipid peroxidation. Lipid peroxidation is a universal feature of oxidative stress, causing loss of cellular structure and function. Under any given conditions, the optimal concentration of SOD is that which decreases chain initiation without elimination of the chain termination properties of the radical, resulting in a minimum of net lipid peroxidation. Mathematical modeling of this hypothesis yields predictions fully consistent with observed laboratory data.
THE POLYACETYLENES FALCARINOL AND FALCARINDIOL AFFECT STRESS RESPONSES IN MYOTUBE CULTURES IN A BIPHASIC MANNER
(2008-09-01) Young, Jette F; Christensen, Lars P; Theil, Peter K; Oksbjerg, Niels
The effects of the bioactive polyacetylenes, falcarinol and falcarindiol, present in carrots, celery, celeriac and other umbelliferous vegetables, on the stress responses in primary myotube cultures, were studied. Biphasic responses on cellular stress responses in myotube cultures were investigated by exposing them to various concentrations of falcarinol and falcarindiol for 24 h before testing effects of 100 μM H2O2 on the intracellular formation of reactive oxygen species (ROS), transcription of the antioxidative enzyme cytosolic glutathione peroxidase (cGPx), and the heat shock proteins (HSP) HSP70 and HO1. At low concentrations (1.6 to 25 μM) polyacetylenes caused a slightly accelerated intracellular ROS formation, increased cGPx transcription and decreased HSP70 and HO1 transcription. The increased cGPx transcription may be interpreted as an adaptive response to the increased ROS formation and may have caused a reduced demand for the protective functions of the HSPs. ROS formation, however, was substantially decreased after pre-incubation with both polyacetylenes at 50 and 100 μM, the cGPx transcription was reduced and the HSP70 and HO1 transcription increased, indicating a need for the protective and repairing functions of the HSPs. In conclusion, pre-incubation with low concentrations of both polyacetylenes prior to H2O2 exposure induced a cytoprotective effect whereas higher concentrations had adverse effects.
EVIDENCE FOR RADIATION HORMESIS AFTER IN VITRO EXPOSURE OF HUMAN LYMPHOCYTES TO LOW DOSES OF IONIZING RADIATION
(2008-09-01) Rithidech, Kanokporn Noy; Scott, Bobby R
Previous research has demonstrated that adding a very small gamma-ray dose to a small alpha radiation dose can completely suppress lung cancer induction by alpha radiation (a gamma-ray hormetic effect). Here we investigated the possibility of gamma-ray hormesis during low-dose neutron irradiation, since a small contribution to the total radiation dose from neutrons involves gamma rays. Using binucleated cells with micronuclei (micronucleated cells) among in vitro monoenergetic-neutron-irradiated human lymphocytes as a measure of residual damage, we investigated the influence of the small gammaray contribution to the dose on suppressing residual damage. We used residual damage data from previous experiments that involved neutrons with five different energies (0.22-, 0.44-, 1.5-, 5.9-, and 13.7-million electron volts [MeV]). Corresponding gamma-ray contributions to the dose were approximately 1%, 1%, 2%, 6%, and 6%, respectively. Total absorbed radiation doses were 0, 10, 50, and 100 mGy for each neutron source. We demonstrate for the first time a protective effect (reduced residual damage) of the small gamma-ray contribution to the neutron dose. Using similar data for exposure to gamma rays only, we also demonstrate a protective effect of 10 mGy (but not 50 or 100 mGy) related to reducing the frequency of micronucleated cells to below the spontaneous level.
LETTER TO THE EDITOR “PROTECTIVE BYSTANDER EFFECTS SIMULATED WITH THE STATE-VECTOR MODEL”—HELA X SKIN EXPOSURE TO 137CS NOT PROTECTIVE BYSTANDER RESPONSE BUT MAMMOGRAM AND DIAGNOSTIC X-RAYS ARE
(2008-09-01) Leonard, Bobby E
The recent Dose Response journal article “Protective Bystander Effects Simulated with the State-Vector Model” (Schollnberger and Eckl 2007) identified the suppressive (below natural occurring, zero primer dose, spontaneous level) dose response for HeLa x skin exposure to 137Cs gamma rays (Redpath et al 2001) as a protective Bystander Effect (BE) behavior. I had previously analyzed the Redpath et al (2001) data with a Microdose Model and conclusively showed that the suppressive response was from Adaptive Response (AR) radio-protection (Leonard 2005, 2007a). The significance of my microdose analysis has been that low LET radiation induced single (i.e. only one) charged particle traversals through a cell can initiate a Poisson distributed activation of AR radio-protection. The purpose of this correspondence is to clarify the distinctions relative to the BE and the AR behaviors for the Redpath groups 137Cs data, show conversely however that the Redpath group data for mammography (Ko et al 2004) and diagnostic (Redpath et al 2003) X-rays do conclusively reflect protective bystander behavior and also herein emphasize the need for radio-biologist to apply microdosimetry in planning and analyzing their experiments for BE and AR. Whether we are adamantly pro-LNT, adamantly anti-LNT or, like most of us, just simple scientists searching for the truth in radio-biology, it is important that we accurately identify our results, especially when related to the LNT hypothesis controversy.