No abstract

Background:In most patients with breast cancer, radiotherapy induces inflammation that is characterised by an increase of promigratory factors in healthy tissues surrounding the tumour. However, their role in the emergence of the migration phenotype and formation of metastases is still unclear.Methods:A single mammary gland of BALB/c mice was irradiated with four doses of 6 Gy given at a 24-h interval. After the last session of irradiation, treated and control mammary glands were either collected for quantification of promigratory and proinflammatory factors or were implanted with fluorescent ubiquitination-based cell cycle indicator (FUCCI)-expressing mouse mammary cancer D2A1 cells. The migration of cancer cells in the mammary glands was monitored by optical imaging. On day 21, mammary tumours and lungs were collected for histology analyses and the quantification of metastases.Results:Pre-irradiation of the mammary gland increased by 1.8-fold the migration of cancer cells, by 2-fold the quantity of circulating cancer cells and by 2.4-fold the number of lung metastases. These adverse effects were associated with the induction of interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2).Conclusion:The emergence of the metastasis phenotype is believed to be associated with the accumulation of mutations in cancer cells. Our results suggest an alternative mechanism based on promigratory factors from irradiated mammary glands. In clinic, the efficiency of radiotherapy could be improved by anti-inflammatory agents that would prevent the stimulation of cancer cell migration induced by radiation.

Two oxygen scavengers have been successfully tested to produce normoxic polymer gel dosimeters under normal atmospheric conditions. The first is ascorbic acid and the second is a chloride (also sulfate) salt of tetrakis (hydroxymethyl) phosphonium. These antioxidants, added to the dosimeter during gel preparation, chemically remove dissolved oxygen that otherwise inhibits propagation of the polymerization reaction during irradiation of the dosimeter. These gel dosimeters are radiosensitive after manufacture under normoxic conditions. However, we show herein that the accuracy of the dosimetric measurement is compromised due to chemical reactions of the antioxidant with radicals. In addition, we provide evidence that both antioxidant and oxygen act as radical scavengers that affect the amount of polymer formed in the gel dosimeter. This can result in important dose inaccuracies in both methacrylic acid-based and acrylamide-based normoxic dosimeter gels.

In the animal model proposed, we demonstrated that irradiation of brain increased the infiltration capacity of F98 cells to the brain, resulting in a reduction of media survival of rats bearing this tumour. This animal model has also allowed identifying inflammatory cytokines and pro-infiltration molecules induced by radiation that can be targeted to prevent this adverse effect of radiation.