Implication of depleted uranium in human carcinogenesis with a glance to implementation of novel and reliable experimental models

The recent acknowledgement of Depleted Uranium (DU) munitions utilization in the Ukrainian conflict has sparked renewed apprehensions regarding the safety of DU, its toxicological profile, and the health ramifications of exposure. Historical data from conflicts like the Gulf War, Bosnia, and Kosovo have recorded an upsurge in neoplastic ailments among soldiers in close proximity to DU deployment. Nevertheless, establishing a direct causal connection between DU exposure and the development of neoplastic diseases remains elusive, as indicated by meta-analyses and studies on animal models. We posit that the absence of a conclusive causal correlation between DU exposure and neoplastic diseases may be ascribed to the constraints of current study models, which fail to encapsulate the intricate interactions between DU and the human immune system, pathophysiology, particularly in the context of chronic, low-level exposure. Nowadays, evidence suggests that DU exposure contributes to a cumulative immunotoxic effect, culminating in a compromised immune surveillance system and an escalated risk of neoplastic diseases over time. To investigate this hypothesis, we advocate for the advancement of pioneering research models, such as human ex-vivo body-on-a-chip systems, which can more accurately replicate the human physiological response to DU exposure and cancer pathophysiology. These models should encompass the examination of immune system modifications along with the potential for DU to interact with diverse organs and tissues, thereby furnishing a more comprehensive understanding of the enduring health impacts of DU.