# Aluminum Genotoxicity in Plants, Mammals, and Unicellular Eukaryotes: The Underlying Mechanisms

**Authors:** Hossein Zakariapour Bahnamiri, Alica Navrátilová, Marek Kovár, Lucia Klongová, Miroslava Požgajová

PMC · DOI: 10.3390/ijms27041665 · International Journal of Molecular Sciences · 2026-02-09

## TL;DR

This paper reviews how aluminum exposure harms plants, mammals, and unicellular organisms by damaging DNA and disrupting cell functions.

## Contribution

The paper systematically reviews genotoxic mechanisms of aluminum across different organisms and identifies cell death pathways.

## Key findings

- Aluminum exposure causes inhibited root growth and disrupted nutrient uptake in plants.
- Aluminum exposure in mammals and humans leads to neurological impairments and bone abnormalities.
- Unicellular organisms experience decreased viability and metabolic disruption due to aluminum.

## Abstract

Aluminum (Al), the third most abundant metal in the Earth’s crust, has been preserved for thousands or even millions of years. However, acidic rain and soil acidification, largely driven by human activities related to industrialization and the increased use of Al in daily life, have led to the mobilization of Al from its complex natural resources. This exposure has affected various microorganisms, including bacteria, fungi, protozoa, and yeast, as well as macroorganisms such as plants, animals, and humans, by introducing them to Al in its ionic form. To date, no biological role for Al has been defined in organisms; however, some beneficial effects have been shown, particularly on plant growth. The exposure of living organisms, particularly human cell lines, to chronic and high doses of Al has been the focus of numerous studies. The consequences of such exposure can vary significantly based on the type of organism, their sensitivity, the form of Al, and the dosage used. In plants, these consequences can include inhibited root growth, stunted development, reduced biomass, and disrupted nutrient uptake. In animals, Al exposure can lead to neurological impairments, impaired mineral metabolism, and bone abnormalities. In humans, it may result in encephalopathy, cognitive deficits, microcytic anemia, and an increased risk of Alzheimer’s disease. Unicellular organisms, such as yeast and bacteria, may experience decreased cell viability, inhibited growth, and disrupted metabolic processes. This review discusses the genotoxicity of Al in plants, mammals, and yeast cells, as well as the subsequent detrimental effects on cell cycle and cell proliferation. It also explores the underlying mechanisms and pathways associated with these effects. Furthermore, the types of Al-induced cell death as a response mechanism to Al toxicity and the pathways involved in various cell types were discussed.

## Linked entities

- **Chemicals:** Aluminum (PubChem CID 123667)
- **Diseases:** Alzheimer’s disease (MONDO:0004975), microcytic anemia (MONDO:0001245)
- **Species:** Homo sapiens (taxon 9606), Bacteria (taxon 2)

## Full-text entities

- **Genes:** GPT2 (glutamic--pyruvic transaminase 2) [NCBI Gene 84706] {aka ALT2, GPT 2, MRT49, NEDSPM}, SIT4 (type 2A-related serine/threonine-protein phosphatase SIT4) [NCBI Gene 851513] {aka PPH1}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, ATM (ATM serine/threonine kinase) [NCBI Gene 472] {aka AT1, ATA, ATC, ATD, ATDC, ATE}, ATM (Serine/Threonine-kinase ATM-like protein) [NCBI Gene 823975] {aka ARABIDOPSIS THALIANA ATAXIA-TELANGIECTASIA MUTATED, ATATM, PIG1, ataxia-telangiectasia mutated, pcd in male gametogenesis 1}, ACT1 (actin) [NCBI Gene 850504] {aka ABY1, END7}, RAD1 (ssDNA endodeoxyribonuclease RAD1) [NCBI Gene 856085] {aka LPB9, RAD12}, SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, CYCS (cytochrome c, somatic) [NCBI Gene 54205] {aka CYC, HCS, THC4}, NUCLEOLIN (nucleolin multifunctional protein) [NCBI Gene 4691] {aka C23, NCL, Nsr1}, CASP9 (caspase 9) [NCBI Gene 842] {aka APAF-3, APAF3, ICE-LAP6, MCH6, PPP1R56}, PMC1 (calcium-transporting ATPase PMC1) [NCBI Gene 852878], ALR1 (Mg(2+) transporter ALR1) [NCBI Gene 853990] {aka SWC3}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, GSN (gelsolin) [NCBI Gene 2934] {aka ADF, AGEL, AMYLD4}, ATR (ATR checkpoint kinase) [NCBI Gene 545] {aka FCTCS, FRP1, MEC1, SCKL, SCKL1}, ced-9 (Apoptosis regulator ced-9) [NCBI Gene 3565776], Actin [NCBI Gene 100811630], CALM1 (calmodulin 1) [NCBI Gene 801] {aka CALML2, CAM2, CAM3, CAMB, CAMC, CAMI}, NPC1 (NPC intracellular cholesterol transporter 1) [NCBI Gene 4864] {aka NPC, POGZ, SLC65A1}, RIPK3 (receptor interacting serine/threonine kinase 3) [NCBI Gene 11035] {aka RIP3}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, PTK2 (protein kinase PTK2) [NCBI Gene 853522] {aka STK2}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, CASP8 (caspase 8) [NCBI Gene 841] {aka ALPS2B, CAP4, Casp-8, FLICE, MACH, MCH5}, RIPK1 (receptor interacting serine/threonine kinase 1) [NCBI Gene 8737] {aka AIEFL, IMD57, RIP, RIP-1, RIP1}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, PLS1 (plastin 1) [NCBI Gene 5357] {aka DFNA76}, PRRT2 (proline rich transmembrane protein 2) [NCBI Gene 112476] {aka BFIC2, BFIS2, DSPB3, DYT10, EKD1, FICCA}, YAP1 (DNA-binding transcription factor YAP1) [NCBI Gene 855005] {aka PAR1, PDR4, SNQ3}, SSO2 (syntaxin) [NCBI Gene 855221], Tubulin [NCBI Gene 547844], ALR2 (putative Mg(2+) transporter ALR2) [NCBI Gene 850494], SLT2 (mitogen-activated serine/threonine-protein kinase SLT2) [NCBI Gene 856425] {aka BYC2, LYT2, MPK1, SLK2}, BECN1 (beclin 1) [NCBI Gene 8678] {aka ATG6, VPS30, beclin1}, TNFRSF1A (TNF receptor superfamily member 1A) [NCBI Gene 7132] {aka CD120a, FPF, TBP1, TNF-R, TNF-R-I, TNF-R55}, MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432] {aka CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2}, CDC40 (Cdc40p) [NCBI Gene 851968] {aka PRP17, SLT15, SLU4}
- **Diseases:** stunted (MESH:D006130), mitochondrial dysfunction (MESH:D028361), injury to (MESH:D014947), neurodegeneration (MESH:D019636), inflammation (MESH:D007249), NOD (MESH:D020191), Alzheimer's disease (MESH:D000544), AL (MESH:D009101), neurotoxicity (MESH:D020258), poisoning (MESH:D011041), Chromosome Aberrations (MESH:D002869), cancer (MESH:D009369), SCID (MESH:D053632), iron dyshomeostasis (MESH:D000090463), impaired mineral metabolism (MESH:D008659), neuroblastoma (MESH:D009447), encephalopathy (MESH:D001927), tumorigenic (MESH:D002471), PCD (MESH:D003643), carcinogenic (MESH:D011230), metastases (MESH:D009362), bone abnormalities (MESH:D001847), Cytotoxicity (MESH:D064420), ePCD (MESH:D018876), Pollen sterility (MESH:D006255), nucleolar dysfunction (MESH:D006331), breast cancer (MESH:D001943), neurological impairments (MESH:D009422), cognitive deficits (MESH:D003072), glioblastoma (MESH:D005909), aneuploidy (MESH:D000782), Al-related disorders (MESH:D019973), microcytic anemia (MESH:C536357), CIN (MESH:D043171), necrosis (MESH:D009336), pheochromocytoma (MESH:D010673)
- **Chemicals:** Phosphate (MESH:D010710), salt (MESH:D012492), deoxyribose (MESH:D003855), oxygen (MESH:D010100), metal (MESH:D008670), GTP (MESH:D006160), abscisic acid (MESH:D000040), nitrogen (MESH:D009584), nucleotide (MESH:D009711), Iron (MESH:D007501), Al oxides (MESH:D000537), aluminum sulfate (MESH:C041524), phospholipids (MESH:D010743), water (MESH:D014867), purines (MESH:D011687), Al acetylacetonate (MESH:C058508), aldehydes (MESH:D000447), CaCl2 (MESH:D002122), glutamate (MESH:D018698), HCl (MESH:D006851), unsaturated fatty acids (MESH:D005231), Al salts (-), hydrogen peroxide (MESH:D006861), AL (MESH:D000535), NEC-1 (MESH:C507699), NO (MESH:D009614), phosphatidylserine (MESH:D010718), sulfhydryl (MESH:D013438), Al acetate (MESH:C013396), lipid (MESH:D008055), aluminum maltolate (MESH:C067527), purine (MESH:C030985), polyamine (MESH:D011073), glutathione (MESH:D005978), citrate (MESH:D019343), AlCl3 (MESH:D000077410), cytokinin (MESH:D003583), Pyrimidines (MESH:D011743), glucose (MESH:D005947), magnesium (MESH:D008274), auxin (MESH:D007210), heavy metals (MESH:D019216), Ca (MESH:D002118), ROS (MESH:D017382), Cd (MESH:D002104), IAA (MESH:C030737)
- **Species:** x Triticosecale (triticale, genus) [taxon 49317], Glycine max (soybean, species) [taxon 3847], Citrus sinensis (apfelsine, species) [taxon 2711], Schizosaccharomyces pombe (fission yeast, species) [taxon 4896], Medicago sativa (alfalfa, species) [taxon 3879], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Helianthus annuus (common sunflower, species) [taxon 4232], Mus musculus (house mouse, species) [taxon 10090], Caenorhabditis elegans (species) [taxon 6239], Citrus (genus) [taxon 2706], Nicotiana tabacum (American tobacco, species) [taxon 4097], Allium sativum (garlic, species) [taxon 4682], Arachis hypogaea (goober, species) [taxon 3818], Triticum turgidum (cone wheat, species) [taxon 4571], Vanrija humicola (species) [taxon 5417], Arabidopsis thaliana (mouse-ear cress, species) [taxon 3702], Pinus massoniana (Chinese red pine, species) [taxon 88730], Vicia faba (broad bean, species) [taxon 3906], Homo sapiens (human, species) [taxon 9606], Rhodotorula taiwanensis RS1 (strain) [taxon 1246992], Rattus norvegicus (brown rat, species) [taxon 10116], Zea mays (maize, species) [taxon 4577], Oryza sativa (Asian cultivated rice, species) [taxon 4530], Triticum aestivum (bread wheat, species) [taxon 4565], Allium cepa (onion, species) [taxon 4679], Hordeum vulgare (barley, species) [taxon 4513], Citrus maxima (buntan, species) [taxon 37334]
- **Mutations:** serine/threonine, cysteine/glutamate, p.Arg399Gln, p.Thr241Met
- **Cell lines:** MR 106-01 — Mus musculus (Mouse), Hybridoma (CVCL_B0CS), NT2 — Mus musculus (Mouse), Malignant neoplasms of the mouse mammary gland, Cancer cell line (CVCL_JA57), SK-N-SH — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0531), U2OS — Homo sapiens (Human), Osteosarcoma, Cancer cell line (CVCL_0042), PC12 — Rattus norvegicus (Rat), Rat adrenal gland pheochromocytoma, Cancer cell line (CVCL_0481), Saos-2 — Homo sapiens (Human), Osteosarcoma, Cancer cell line (CVCL_0548), BY-2 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_A628), Neuro-2a — Mus musculus (Mouse), Mouse neuroblastoma, Cancer cell line (CVCL_0470), T98G — Homo sapiens (Human), Glioblastoma, Cancer cell line (CVCL_0556), SH-SY5Y — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0019), V79 — Cricetulus griseus (Chinese hamster), Spontaneously immortalized cell line (CVCL_2234)

## Full text

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## References

167 references — full list in the complete paper: https://tomesphere.com/paper/PMC12940377/full.md

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Source: https://tomesphere.com/paper/PMC12940377