Chemotherapy-induced toxicity—a secondary effect caused by released DNA?

The use of chemotherapy treatment is often limited by toxic side-effects caused to healthy cells. In general, most chemotherapy treatments cause DNA damage or stop cells in mitosis, targeting both dividing cancer and dividing healthy cells (e.g. gut epithelium, bone marrow, hair follicle). Clearly, DNA damaging chemotherapy treatments may cause damage to both cancer and healthy cells to generate toxic side-effects (Figure 1A). In a new study presented in this issue of Annals of Oncology, Mittra et al. challenge this concept and suggest that released cell-free chromatin (cfCh) may itself cause inflammation and DNA damage as a secondary event [1] (Figure 1B). The authors also demonstrate that treatment with DNAse I or the DNA-degrading agent Resveratrol-Cu may suppress some chemotherapy-induced neutropenia, inflammation and DNA damage markers in multiple organs and in peripheral blood mononuclear cells. The authors demonstrated suppressed toxicity by all five different chemotherapy treatments used, i.e. adriamycin, cyclophosphamide, cisplatin, methotrexate and paclitaxel. Although caution should be taken when interpreting the results since this is a small limited animal study, the implication could be that DNA neutralizing agents may prevent chemotherapy-induced toxicities.

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