Thresholds and transitions for activation of cellular radioprotective mechanisms - correlations between HRS/IRR and the 'inverse' dose-rate effect.
OBJECTIVE
In biophysical modeling for several instances of radiation-induced radioprotection, i.e., adaptive response (AR), hyper-radiosensitivity and induced radioresistance (HRS/IRR), and the inverse dose-rate effect (IDRE), empirical fits are premised for the thresholds and transitions of the radioprotection. We provide realistic model formulations for the observed behaviors, which we apply to both HRS/IRR and IDRE.


METHODS
We use homeostatic balance equations, including cell biophysical endogenic adjustments (originating from within the cell), providing a radiation-induced 'trigger' or continuous thresholds and transitions.


RESULTS
A 'trigger' threshold requires an instantaneous, step function. Current HRS/IRR transition model does not provide 'triggered' threshold but continuous progression from high sensitivity to reduced radiosensitivity, although the investigators premise 'trigger' behavior. IDRE data suggest 'triggered' thresholds at discrete dose rates. It appears that HRS/IRR and IDRE at low dose and dose rate intentionally provide protection against potentially carcinogenic mutations.


CONCLUSIONS
The homeostatic formulation shows, when applied to the IRR using a dose and dose rate dependent Linear-Quadratic model (LQ2), that the IRR protection is 'triggered' at a discrete low dose and induced by a transitory increase in the damage repair rate constant in the LQ2 model of the single event, linear response, radiation damage. Since both IDRE and IRR have 'triggered' thresholds and as a result of increased endogenic damage recognition, increased mobilization of repair resources, activation of cell cycle arrest and/or increased repair rate, we premise that both may be from the same endogenic radioprotection biochemical mechanisms.
Leonard
Bobby E
BE
International Academy of Hi-Tech Services, Inc., Severna Park, Maryland 21146, USA. vfleonard@worldnet.att.net
D000818:Animals; D001703:Biophysics / Q000379:methods; D002453:Cell Cycle / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D002875:Chromosomes / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D006367:HeLa Cells; D006801:Humans; D008962:Models, Theoretical; D016296:Mutagenesis; D011836:Radiation Tolerance; D011874:Radiometry / Q000379:methods*