Latest on Radiation-Induced Carcinogenesis

Monday, October 17, 2005 10:15 AM-12:00 PM Room No. 610/612
Chair(s): Barcellos-Hoff, Mary Helen

(SY024) Cancer and low dose responses in vivo: Implications for radiation protection.

Mitchel, Ron*,1, 1 Radiation Biology and Health Physics, Chalk River, Ontario, Canada

ABSTRACT- Radiation protection practices assume that cancer risk is linearly proportional to total dose, without a threshold, both for people with normal cancer risk and for people who may be cancer prone for genetic reasons. Mice heterozygous for Tp53 are cancer prone, and their increased risk from high doses given at high or low dose rates was not different from Tp53 normal mice. However, in Tp53 normal or heterozygous mice, a single low, whole body dose of low LET radiation given at low dose rate one day prior to a large, cancer-initiating dose reduced risk by increasing cancer latency. In Tp53 heterozygotes, both the magnitude of protection and the dose threshold at which protective effects turned to detrimental effects was lower than in animals with full Tp53 function. In the cancer prone mice, a single low dose alone, in the absence of a second large cancer-inducing dose, protected against spontaneous cancer, again by increasing tumor latency. Increased tumor latency without a cancer frequency change implies that low doses in vivo primarily slow the process of genomic instability, consistent with the characteristic elevated capacity for correct DSB rejoining seen in low dose exposed cells. The in vivo animal data indicates that, for low doses and low dose rates in both normal and cancer prone adult mice, risk does not increase linearly with dose, and dose thresholds for increased risk exist. Below those dose thresholds (which are influenced by Tp53 function) overall risk is reduced below that of the unexposed control mice, indicating that Dose Rate Effectiveness Factors (DREF) may approach infinity, rather than the current assumption of 2. However, as dose decreases, different tissues appear to have different thresholds at which detriment turns to protection, indicating that individual tissue weighting factors (Wt) are also not constant, but vary from positive values to zero with decreasing dose. Measurements of Relative Biological Effect between high and low LET radiations are used to establish the radiation weighting factors (Wr) applied in radiation protection, and these are also assumed to be constant with dose. However, since the risk from an exposure to low LET radiation is not constant with dose, it would seem unlikely that radiation-weighting factors for high LET radiation are actually constant at low dose and dose rate.

Key words: cancer, low-dose, risk, mice

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2005 RRS