Journal Issue:
Dose-Response: An International Journal: Volume 7, Issue 3

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2009-30-09
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Dose-Response Vol 7, no 3, Cover
(2009-09-01)
Publication
MODIFICATION IN THE EXPRESSION OF MRE11/RAD50/NBS1 COMPLEX IN LOW DOSE IRRADIATED HUMAN LYMPHOCYTES
(2009-09-01) Singh, Sompal; Bala, Madhu; Kumar, Raj; Kumar, Anil; Dhiman, SC
Despite the fact that high doses of radiation are detrimental, low dose radiation (LDR) often protects the organism against a subsequent exposure of lethal doses of radiation. Present study was undertaken to understand the role of Mre11, Rad50 and Nbs1 genes in the low dose radio-adapted human peripheral blood mononuclear cells (PBMCs). Optimum time interval between low dose (0.07 Gy) and high dose (5.0 Gy) of 60Co-γ-radiation was observed to be 5.0 hours, at which PBMCs showed maximum LDR induced resistance (RIR). At cytogenetic level, micronuclei frequency was found to be reduced in LDR pre-irradiated PBMCs subsequently exposed to high dose radiation (HDR) as compared to controls. At transcriptional level, with reference to sham-irradiated cells significantly (p≤0.05) altered expression of Mre11, Rad50 and Nbs1 genes was observed in low dose irradiated cells. At protein level, Mre11, Rad50 and Nbs1 were enhanced significantly (p≤0.05) in low dose pre-irradiated cells subsequently exposed to high dose of radiation as compared to only high dose irradiated cells. Transcriptional as well as translational modulation in the expression of MRN complex components upon low dose irradiation may confer its participation in repair pathways, resulting in induced resistance.
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THE EMERGING LOW-DOSE THERAPY FOR ADVANCED CANCERS
(2009-09-01) Satti, Jahangir
Generally minute doses of drugs have been prescribed in biotherapies, homeopathy, immunization and vaccinations for centuries. Now the use of low doses of drugs is on the rise to combat serious diseases such as advanced cancers around the world. This new therapeutic approach to address solid tumors and other advanced diseases is a departure from the conventional use of maximum dose protocol. A small dose of the prescribed drug is frequently administered in a continuous fashion, at regular intervals, either as a standard treatment or as a maintenance therapy for a long time. However, this new treatment method lacks any standard for drug quantization, dose fractionation, repetition frequency and duration of a treatment course for an individual patient. This paper reviews literature about metronomic therapy and discusses hormesis: both phenomena occur in low dose ranges. Better mathematical models, computer simulations, process optimization and clinical trials are warranted to fully exploit the potential of low dose metronomic therapy to cure chronic and complicated diseases. New protocols to standardize metronomic dosimetry will answer the age old questions related to hormesis and homeopathy. It appears that this new low-dose metronomic therapy will have far reaching effects in curing chronic diseases throughout the world.
Publication
INTERPRETING ‘DOSE-RESPONSE’ CURVES USING HOMEODYNAMIC DATA: WITH AN IMPROVED EXPLANATION FOR HORMESIS
(2009-09-01) Stebbing, ARD
A re-interpretation of the ‘dose-response’ curve is given that accommodates homeostasis. The outcome, or overall effect, of toxicity is the consequence of toxicity that is moderated by homeodynamic responses. Equilibrium is achieved by a balance of opposing forces of toxic inhibition countered by a stimulatory response. A graphical model is given consisting of two linked curves (response vs concentration and effect vs concentration), which provide the basis for a re-interpretation of the ‘dose-response’ curve. The model indicates that such relationships are non-linear with a threshold, which is due to homeodynamic responses. Subthreshold concentrations in ‘dose-response’ curves provide the sum of toxic inhibition minus the homeodynamic response; the response itself is unseen in serving its purpose of neutralizing perturbation. This interpretation suggests why the α- and β-curves are non-linear. The β-curve indicates adaptive overcorrection to toxicity that confers greater resistance to subsequent toxic exposure, with hormesis as an epiphenomenon.
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