Emerging health risks and underlying toxicological mechanisms of uranium contamination: Lessons from the past two decades.

Uranium contamination is a global health concern. Regarding natural or anthropogenic uranium contamination, the major sources of concern are groundwater, mining, phosphate fertilizers, nuclear facilities, and military activities. Many epidemiological and laboratory studies have demonstrated that environmental and occupational uranium exposure can induce multifarious health problems. Uranium exposure may cause health risks because of its chemotoxicity and radiotoxicity in natural or anthropogenic scenarios: the former is generally thought to play a more significant role with regard to the natural uranium exposure, and the latter is more relevant to enriched uranium exposure. The understanding of the health risks and underlying toxicological mechanisms of uranium remains at a preliminary stage, and many controversial findings require further research. In order to present state-of-the-art status in this field, this review will primarily focus on the chemotoxicity of uranium, rather than its radiotoxicity, as well as the involved toxicological mechanisms. First, the natural or anthropogenic uranium contamination scenarios will be briefly summarized. Second, the health risks upon natural uranium exposure, for example, nephrotoxicity, bone toxicity, reproductive toxicity, hepatotoxicity, neurotoxicity, and pulmonary toxicity, will be discussed based on the reported epidemiological cases and laboratory studies. Third, the recent advances regarding the toxicological mechanisms of uranium-induced chemotoxicity will be highlighted, including oxidative stress, genetic damage, protein impairment, inflammation, and metabolic disorder. Finally, the gaps and challenges in the knowledge of uranium-induced chemotoxicity and underlying mechanisms will be discussed.