The link between the products of synthetic chemistry and cancer is at the heart of much research. Recent work has identified the use of plant protection agents by farmers as a risk factor for developing non-Hodgkin lymphoma, including diffuse large B cell lymphoma (DLBCL) is the most common histology. Different biological models were used to understand the role of pesticides in lymphomagenesis. To summarize, most pesticides act at the cellular and molecular level, on different signaling pathways. After metabolized by cytochrome P450, these compounds generally become pro-oxidants. The increase in reactive oxygen species rate (SAR) causes the activation of signaling pathways involved in cell proliferation and survival. But deregulation of oxidative status does not in itself justify the specificity of the impact of pesticides on specific pathologies. Several agents have a genotoxic effect, others induce the activation of signaling pathways by binding to transcription factors and others have immunomodulating properties.
Among these four mechanisms by which pesticides are involved in lymphomagenesis, two are also associated with resistance to chemotherapy. Thus, genotoxic agents leads the implementation process of DNA repair, used to repair genotoxic lesions induced by chemotherapeutic agents and evade apoptosis. On the other hand, to survive a high level of ROS, the tumor cell raises the level of antioxidant defenses, maintaining redox homeostasis and preventing oxidative stress. However, a high production of antioxidants constitutes a barrier to the effectiveness of anti-tumor agents which are effective in the generation of oxidative stress.
