How Does Uranium Induce Pathogenic Changes?

Learning Objectives

Upon completion of this section you will be able to

  • identify the mechanism by which uranium induces pathogenic changes.

The body of evidence points to both natural and depleted uranium as being primarily chemical toxicants, with radiation playing a minor role or no role at all. Uranium has not been associated with human cancer, but if cancer were to occur, bone would be the most likely location.

The primary target of uranium exposure is the kidney. However, most of the effects noted in humans have been due to high acute exposures. There is human evidence that kidney damage caused by occupational uranium overexposure can eventually heal after the excessive exposure ends [Hursh and Spoor 1973]. Uranium can cause acute renal failure in experimental models, and the pathologic changes are consistent with acute tubular necrosis. Recent studies in humans have not shown the same nephrotoxic effects as those in experimental animal studies [Kurttio et al. 2002, 2006].


A well-accepted theory for renal toxicity is the release of uranium from serum bicarbonate complex in the kidney that allows uranium to bind to available phosphate and protein. Irritation from overexposure produces most damage in the proximal convoluted tubule, followed by the glomerulus. Another theory includes uranium inhibition of mitochondrial ATPase activity and sodium transport mechanisms that can reduce the functionality and repair capacity of the epithelium [Keith et al. 2007].

The mechanism for lung damage is deep lung irritation that can degrade into fibrosis or emphysema. This can be associated with oxidative stress, altered gene expression, and inhibition of sodium-dependent phosphate and glucose transport systems [Keith et al. 2007].

Primary Sites Affected

Uranium exposure primarily affects the kidneys (renal tubules), and inhalation exposure can also affect the lungs (alveolar changes).


Alpha radiation, such as that from uranium, has been designated a human carcinogen. Therefore, since uranium is radioactive, exposure to uranium increases a person’s calculated risk of developing cancer. However, the Committee on the Biological Effects of Ionizing Radiation (BEIR IV) reported that eating food or drinking water that has background amounts of uranium will most likely not cause cancer or other health problems in most people. No human cancer of any type has ever been seen as a result of exposure to natural or depleted uranium. The chance of developing cancer is greater with exposure to enriched uranium, because it is more radioactive than natural uranium [ATSDR 2008b].

The primary mechanism of toxicity would be direct damage to DNA from alpha particle interactions. If cancer were to occur, the most likely site would be bone (resulting in bone sarcomas). However, as previously mentioned, cancer has not been associated with uranium exposure.

The International Agency for Research on Cancer (IARC) and the U.S. National Toxicology Program (NTP) have no carcinogenicity ratings for uranium. The U.S. Environmental Protection Agency has withdrawn its carcinogenicity classification for uranium. The National Institute of Occupational Safety and Health (NIOSH) considers insoluble and soluble uranium compounds to be potential occupational carcinogens as defined by the U.S. Occupational Safety and Health Administration (OSHA) carcinogen policy [29 CFR 1990]. For more information, please see NIOSH’s Uranium (soluble compounds, as U) [NIOSH 1996].

The American Conference of Industrial Hygienists (ACGIH) considers insoluble and soluble uranium compounds Confirmed Human Carcinogens (A1).

Carcinogenicity ratings are summarized on these OSHA websites:

Cancer among uranium miners has not been associated with exposure to uranium, but instead with exposure to radon progeny, diesel exhaust particles, arsenic, and other elements in the mine air which they breathe [ATSDR 1999 (updated 2008)].

Key Points
  • The process believed to account for uranium’s pathogenicity is uranium ion effects in the kidneys.
  • Alpha radiation (such as that from uranium) is classified as a human carcinogen. However, human studies have not found elevated rates of cancer from uranium exposure, and high-dose animal studies have not found cancer following inhalation, oral, or dermal exposure to uranium.