Biological-Based Modeling of Low Dose Radiation Risks
The objective of this project was to refine a biological-based model (called NEOTRANS2) for low-dose, radiation-induced stochastic effects taking into consideration newly available data, including data on bystander effects (deleterious and protective). The initial refinement led to our NEOTRANS3 model which has undergone further refinement (e.g., to allow for differential DNA repair/apoptosis over different dose regions). The model has been successfully used to explain nonlinear dose-response curves for low-linear-energy-transfer (LET) radiation-induced mutations (in vivo) and neoplastic transformation (in vitro). Relative risk dose-response functions developed for neoplastic transformation have been adapted for application to cancer relative risk evaluation for irradiated humans. Our low-dose research along with that conducted by others collectively demonstrate the following regarding induced protection associated with exposure to low doses of low-LET radiation: (1) protects against cell killing by high-LET alpha particles; (2) protects against spontaneous chromosomal damage; (3) protects against spontaneous mutations and neoplastic transformations; (4) suppresses mutations induced by a large radiation dose even when the low dose is given after the large dose; (5) suppresses spontaneous and alpha-radiation-induced cancers; (6) suppresses metastasis of existing cancer; (7) extends tumor latent period; (8) protects against diseases other than cancer; and (9) extends life expectancy. These forms of radiation-induced protection are called adapted protection as they relate to induced adaptive response. Thus, low doses and dose rates of low-LET radiation generally protect rather than harm us. These findings invalidate the linear not threshold (LNT) hypothesis which is based on the premise that any amount of radiation is harmful irrespective of its type. The hypothesis also implicates a linear dose-response curve for cancer induction that has a positive slope and no threshold. However, low-dose and low-dose-rate induced adapted protection leads to hormetic type dose-response relationships (e.g. U or J shaped) for cancer induction. Indeed, our research findings point to several dose zones of biological responses: (1) The natural background radiation dose zone over which increasing background radiation doses appear to lead to decrease cancer risk (Transition Zone A) due to activation (in a stochastic manner) of a system of protective processes that include high-fidelity DNA repair, apoptosis of unstable cells, and immune system activation. (2) A dose zone just above natural background radiation exposure over which cancer risk appears to further decrease and then remain suppressed at a relatively constant level below the spontaneous frequency (Zone of Maximal Protection); (3) higher but moderate doses over which cancer risk increases rather steeply over relative narrow dose range (Transition Zone B) due to radiation related suppression of protective processes (immune system function and selective apoptosis of unstable cells); (4) higher doses (LNT zone) where cancer risk increases as a linear function of dose for a range of doses (protective processes maximally suppressed in this zone). The indicted dose zones are dose-rate and radiation-type dependent with the protective zone increasing as dose rate is decreases and exposure time extended. In fact, natural background low-LET radiation appears to be protecting us not only from cancer occurrence but also from other genomic instability associated diseases via repeatedly inducing transient adapted protection. Reducing natural background radiation exposure (e.g., via relocation) over extended periods (years) would be expected to cause more harm than benefit. The harm would be expressed as increased cases of cancer and other genomic-instability-associated diseases as well as in significantly reduced life expectancy.
- Research Organization:
- Lovelace Biomedical & Environmental Research Institute
- Sponsoring Organization:
- USDOE Office of Science (SC)
- DOE Contract Number:
- FG02-03ER63671
- OSTI ID:
- 894721
- Report Number(s):
- DOE/ER/63671-1
- Country of Publication:
- United States
- Language:
- English
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