Carcinogenesis Associated with Toxin Nephropathy: Proposed Mediation by Phosphate Toxicity
Although cancer is often considered a genetic disease, genotoxic damage to nuclear DNA caused by carcinogens is not always sufficient to stimulate cancer cell growth, suggesting that other etiological factors are involved. Indeed, many carcinogens are also nephrotoxic and can impair kidney function....
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MDPI AG
2025-06-01
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| author | Ronald B. Brown John G. Mielke |
| author_facet | Ronald B. Brown John G. Mielke |
| author_sort | Ronald B. Brown |
| collection | DOAJ |
| description | Although cancer is often considered a genetic disease, genotoxic damage to nuclear DNA caused by carcinogens is not always sufficient to stimulate cancer cell growth, suggesting that other etiological factors are involved. Indeed, many carcinogens are also nephrotoxic and can impair kidney function. In turn, impaired renal function can dysregulate serum inorganic phosphate, leading to hyperphosphatemia and excess phosphate storage in tissues, which causes phosphate toxicity. Moreover, phosphate toxicity can contribute to cancer cell growth by activating cell signaling pathways, overexpressing sodium phosphate cotransporters, and stimulating excessive RNA biogenesis and protein synthesis. The present narrative review proposes a general underlying mechanism by which phosphate toxicity mediates the association of toxin nephropathy with carcinogenesis. This proposed pathway could explain why any factor that impairs renal function, including an overload of nontoxic substances, may indirectly contribute to excess phosphate sequestration in the tumor microenvironment which stimulates cancer cellular growth. Importantly, chemotherapy agents are often nephrotoxic, and carcinogenicity associated with such nephrotoxins could explain the occurrence of second tumors in treated cancer patients. More research is needed to investigate the mediating role of phosphate toxicity in the association of toxin nephropathy with carcinogenesis. |
| format | Article |
| id | doaj-art-90e8d8a919744d9ab43ff747cb8a064d |
| institution | OA Journals |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj-art-90e8d8a919744d9ab43ff747cb8a064d2025-08-20T02:35:59ZengMDPI AGCells2073-44092025-06-01141395210.3390/cells14130952Carcinogenesis Associated with Toxin Nephropathy: Proposed Mediation by Phosphate ToxicityRonald B. Brown0John G. Mielke1Waterloo Institute for Complexity and Innovation, University of Waterloo, Waterloo, ON N2L 3G1, CanadaSchool of Public Health Sciences, University of Waterloo, Waterloo, ON N2L 3G1, CanadaAlthough cancer is often considered a genetic disease, genotoxic damage to nuclear DNA caused by carcinogens is not always sufficient to stimulate cancer cell growth, suggesting that other etiological factors are involved. Indeed, many carcinogens are also nephrotoxic and can impair kidney function. In turn, impaired renal function can dysregulate serum inorganic phosphate, leading to hyperphosphatemia and excess phosphate storage in tissues, which causes phosphate toxicity. Moreover, phosphate toxicity can contribute to cancer cell growth by activating cell signaling pathways, overexpressing sodium phosphate cotransporters, and stimulating excessive RNA biogenesis and protein synthesis. The present narrative review proposes a general underlying mechanism by which phosphate toxicity mediates the association of toxin nephropathy with carcinogenesis. This proposed pathway could explain why any factor that impairs renal function, including an overload of nontoxic substances, may indirectly contribute to excess phosphate sequestration in the tumor microenvironment which stimulates cancer cellular growth. Importantly, chemotherapy agents are often nephrotoxic, and carcinogenicity associated with such nephrotoxins could explain the occurrence of second tumors in treated cancer patients. More research is needed to investigate the mediating role of phosphate toxicity in the association of toxin nephropathy with carcinogenesis.https://www.mdpi.com/2073-4409/14/13/952carcinogennephrotoxintoxin nephropathyphosphate toxicitydysregulated renal functiontumor microenvironment |
| spellingShingle | Ronald B. Brown John G. Mielke Carcinogenesis Associated with Toxin Nephropathy: Proposed Mediation by Phosphate Toxicity Cells carcinogen nephrotoxin toxin nephropathy phosphate toxicity dysregulated renal function tumor microenvironment |
| title | Carcinogenesis Associated with Toxin Nephropathy: Proposed Mediation by Phosphate Toxicity |
| title_full | Carcinogenesis Associated with Toxin Nephropathy: Proposed Mediation by Phosphate Toxicity |
| title_fullStr | Carcinogenesis Associated with Toxin Nephropathy: Proposed Mediation by Phosphate Toxicity |
| title_full_unstemmed | Carcinogenesis Associated with Toxin Nephropathy: Proposed Mediation by Phosphate Toxicity |
| title_short | Carcinogenesis Associated with Toxin Nephropathy: Proposed Mediation by Phosphate Toxicity |
| title_sort | carcinogenesis associated with toxin nephropathy proposed mediation by phosphate toxicity |
| topic | carcinogen nephrotoxin toxin nephropathy phosphate toxicity dysregulated renal function tumor microenvironment |
| url | https://www.mdpi.com/2073-4409/14/13/952 |
| work_keys_str_mv | AT ronaldbbrown carcinogenesisassociatedwithtoxinnephropathyproposedmediationbyphosphatetoxicity AT johngmielke carcinogenesisassociatedwithtoxinnephropathyproposedmediationbyphosphatetoxicity |