Cancer cells metabolically "fertilize" the tumor microenvironment with hydrogen peroxide, driving the Warburg effect : Implications for PET imaging of human tumors

The radiation induced bystander effect is a well-accepted consequence of ionizing radiation exposure. However, it has become clear that bystander responses in vitro can result from a number of stress stimuli. We had reported that media conditioned on tumor cell cultures induced a bystander effect in recipient normal cell cultures and asked whether an analogous process could occur in vivo-could the presence of a tumor induce DNA damage in distant tissues. We recently demonstrated the presence of a distant bystander DNA damage response in vivo in the gastrointestinal organs and skin of mice implanted with subcutaneous tumors. The activation of inflammatory macrophages through the cytokine CCL2 was found to be required for this distant genotoxic response. These results shed new light on the consequences of tumor growth to distant parts of the body and highlight the potential for possible medical interventions to mitigate the effect of cancers.