There are many studies showing the effects of fluoride on p53 expression. A short list is provided below.
Barbier O, Arreola-Mendoza L, Del Razo LM - "Molecular mechanisms of fluoride toxicity" Chem Biol Interact 188(2):319-33 (2010) doi: 10.1016/j.cbi.2010.07.011
Caglayan C, Kandemir FM, Darendelioğlu E, Küçükler S, Ayna A - "Hesperidin protects liver and kidney against sodium fluoride-induced toxicity through anti-apoptotic and anti-autophagic mechanisms" Life Sci 281:119730 (2021) doi: 10.1016/j.lfs.2021.119730
https://pubmed.ncbi.nlm.nih.gov/34147482/
Chen Q, Wang Z, Xiong Y, Zou X, Liu Z - "Comparative study of p38 MAPK signal transduction pathway of peripheral blood mononuclear cells from patients with coal-combustion-type fluorosis with and without high hair selenium levels" Int J Hyg Environ Health 213(5):381-6 (2010) doi: 10.1016/j.ijheh.2010.06.002 [co-factor selenium]
"The mRNA and protein level of p53 was significantly higher in high fluoride+high selenium group than that in other two groups."
Deng H, Fujiwara N, Cui H, Whitford GM, Bartlett JD, Suzuki M - "Histone acetyltransferase promotes fluoride toxicity in LS8 cells" Chemosphere. 247:125825 (2020). doi: 10.1016/j.chemosphere.2020.125825
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863547/
"Here we demonstrate that fluoride activates histone acetyltransferases (HATs) including CBP, p300, PCAF and Tip60 to acetylate p53."
Geng N, Dong S, Xie P, Zhang Y, Shi R, Chen C, Xu Z, Chen Q - "Excessive fluoride induces ovarian function impairment by regulating levels of ferroptosis in fluorosis women and ovarian granulosa cells" Reprod Toxicol 125:108556 (2024). doi: 10.1016/j.reprotox.2024.108556
https://linkinghub.elsevier.com/retriev ... 24)00023-6
"It is concluded therefore that NaF increases the expression of p53 and inhibits ovarian granulosa cell ferroptosis preventive protein expression, resulting in abnormal hormone secretion and the ovarian dysfunction."
Gutiérrez-Salinas J, Morales-González JA, Madrigal-Santillán E, Esquivel-Soto J, Esquivel-Chirino C, González-Rubio MG, Suástegui-Domínguez S, Valadez-Vega C - "Exposure to sodium fluoride produces signs of apoptosis in rat leukocytes" Int J Mol Sci 11(9):3610-22 (2010) doi: 10.3390/ijms11093610
https://www.mdpi.com/1422-0067/11/9/3610
Ha J, Chu Q, Wang A, Xia T, Yang K - "Effects on DNA damage and apoptosis and p53 protein expression induced by fluoride in human embryo hepatocytes" Journal of Hygiene Research 33(4):400-2 (2004)
https://pubmed.ncbi.nlm.nih.gov/15461257/
"Fluoride can increase the rate of DNA damage, and induce apoptosis and expression of p53 in human embryo hepatocytes. Furthermore, both apoptosis and the level of p53 expression, there exists a rise tendency with the increase concentration of fluoride."
Korkmaz R, Yüksek V, Dede S - "The Effects of Sodium Fluoride (NaF) Treatment on the PI3K/Akt Signal Pathway in NRK-52E Cells" Biol Trace Elem Res. 200(7):3294-3302 (2022) doi: 10.1007/s12011-021-02927-4
https://link.springer.com/article/10.10 ... 21-02927-4
"According to the results obtained in the study, the low NaF concentration increased the expression levels of the ERBB2, PI3K, and Akt genes, while the higher concentrations did not significantly affect these levels. The expression of mTOR decreased at all given concentrations. The expression of the TP53 gene did not change at the low concentration, while it increased at the high concentrations."
Liu H, Luo Q, Cui H, Deng H, Kuang P, Lu Y, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L - "Sodium fluoride causes hepatocellular S-phase arrest by activating ATM-p53-p21 and ATR-Chk1-Cdc25A pathways in mice" Oncotarget 9(4):4318-4337 (2017) doi: 10.18632/oncotarget.23093
https://www.oncotarget.com/article/23093/text/
Liu Y, Sun B, Zhang S, Li J, Qi J, Bai C, Zhang J, Liang S - "Glycine alleviates fluoride-induced oxidative stress, apoptosis and senescence in a porcine testicular Sertoli cell line" Reprod Domest Anim 56(6):884-896 (2021) doi: 10.1111/rda.13930
https://onlinelibrary.wiley.com/doi/10.1111/rda.13930
"The mRNA expression levels of P53, P21, HMGA2 and P16INK4a were significantly increased in NaF-exposed cells compared with those in the control and glycine groups."
Luo Q, Guo H, Kuang P, Cui H, Deng H, Liu H, Lu Y, Wei Q, Chen L, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L - "Sodium Fluoride Arrests Renal G2/M Phase Cell-Cycle Progression by Activating ATM-Chk2-P53/Cdc25C Signaling Pathway in Mice" Cell Physiol Biochem 51(5):2421-2433 (2018). doi: 10.1159/000495899
https://karger.com/cpb/article/51/5/242 ... Phase-Cell
Mondal P, Shaw P, Dey Bhowmik A, Bandyopadhyay A, Sudarshan M, Chakraborty A, Chattopadhyay A - "Combined effect of arsenic and fluoride at environmentally relevant concentrations in zebrafish (Danio rerio) brain: Alterations in stress marker and apoptotic gene expression" Chemosphere. 269:128678 (2021). doi: 10.1016/j.chemosphere.2020.128678.
https://www.sciencedirect.com/science/a ... 3520328733
"This preliminary study indicates an antagonistic effect of these two toxicants in zebrafish brain and needs further studies involving oxidative stress independent markers to understand the detailed molecular mechanism."
Ouyang Z, Yang B, Yi J, Zhu S, Lu S, Liu Y, Li Y, Li Y, Mehmood K, Hussain R, Ijaz M, Guo J, Tang Z, Li Y, Zhang H - "Exposure to Fluoride induces apoptosis in liver of ducks by regulating Cyt-C/Caspase 3/9 signaling pathway" Ecotoxicol Environ Saf 224:112662 (2021) doi: 10.1016/j.ecoenv.2021.112662
https://www.sciencedirect.com/science/a ... 1321007740
"The results showed that protein expression levels of Bax and p53 were increased while protein expression level of Bcl-2 was reduced in treated ducks."
Qing-Feng S, Ying-Peng X, Tian-Tong X - "Matrix metalloproteinase-9 and p53 involved in chronic fluorosis induced blood-brain barrier damage and neurocyte changes" Arch Med Sci 15(2):457-466 (2019) doi: 10.5114/aoms.2019.83294
https://www.archivesofmedicalscience.co ... 0,0,2.html
"Increased p53 may be one of the factors causing damage."
Ramesh N, Vuayaraghavan AS, Desai BS, Natarajan M, Murthy PB, Pillai KS - "Low levels of p53 mutations in Indian patients with osteosarcoma and the correlation with fluoride levels in bone" J Environ Pathol Toxicol Oncol 20(3):237-43 (2001)
https://pubmed.ncbi.nlm.nih.gov/11797833/
"The high levels of bone fluoride levels and the similarity of the mechanisms of action between fluoride-induced DNA damage and chemically-induced p53 mutations lead us to propose that high fluoride bone content might have been one of the major factors causing osteosarcoma."
Song C, Shi D, Chang K, Li X, Dong Q, Ma X, Wang X, Guo Z, Liu Y, Wang J - "Sodium fluoride activates the extrinsic apoptosis via regulating NOX4/ROS-mediated p53/DR5 signaling pathway in lung cells both in vitro and in vivo" Free Radic Biol Med 169:137-148 (2021) doi: 10.1016/j.freeradbiomed.2021.04.007
https://www.sciencedirect.com/science/a ... 4921002094
Sun Z, Zhang W, Li S, Xue X, Niu R, Shi L, Li B, Wang X, Wang J - "Altered miRNAs expression profiling in sperm of mice induced by fluoride" Chemosphere 155:109-114 (2016) doi: 10.1016/j.chemosphere.2016.04.053
https://www.sciencedirect.com/science/a ... 3516305276
Suzuki M, Ikeda A, Bartlett JD - "Sirt1 overexpression suppresses fluoride-induced p53 acetylation to alleviate fluoride toxicity in ameloblasts responsible for enamel formation" Arch Toxicol 92(3):1283-1293 (2018). doi: 10.1007/s00204-017-2135-2
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667832/
"This is the first report implicating acetylation of p53 followed by Cdkn1a/p21 expression in fluoride toxicity. Our results support the hypothesis that SIRT1 plays a role in the adaptive response protecting against fluoride toxicity in ameloblast-derived cells. The SIRT1/p53 pathway may be a potential therapeutic target for dental fluorosis."
Tu W, Zhang Q, Liu Y, Han L, Wang Q, Chen P, Zhang S, Wang A, Zhou X - "Fluoride induces apoptosis via inhibiting SIRT1 activity to activate mitochondrial p53 pathway in human neuroblastoma SH-SY5Y cells" Toxicol Appl Pharmacol 347:60-69 (2018) doi: 10.1016/j.taap.2018.03.030
https://www.sciencedirect.com/science/a ... 8X18301224
"Fluoride inhibited the deacetylase activity of SIRT1 and increased p53 (acetyl K382) level in SH-SY5Y cells."
Wang D, Yin K, Zhang Y, Lu H, Hou L, Zhao H, Xing M - "Novel pathways of fluoride-induced hepatotoxicity: P53-dependent ferroptosis induced by the SIRT1/FOXOs pathway and Nrf2/HO-1 pathway" Comp Biochem Physiol C Toxicol Pharmacol 264:109526 (2022). doi: 10.1016/j.cbpc.2022.109526.
https://pubmed.ncbi.nlm.nih.gov/36455829/
Wang AG, Chu QL, He WH, Xia T, Liu JL, Zhang M, Nussler AK, Chen XM, Yang KD - "Effects on protein and mRNA expression levels of p53 induced by fluoride in human embryonic hepatocytes" Toxicol Lett 158(2):158-63 (2005) doi: 10.1016/j.toxlet.2005.03.010 [U-shape]
https://www.sciencedirect.com/science/a ... 7405001025
"The mRNA expression levels of p53 in the fluoride groups were markedly higher than in the control group. The mRNA expression level of p53 in the high dose fluoride group was however lower compared to the middle dose fluoride group, but similar to the low dose fluoride group. These finding suggest that fluoride can decrease the L-02 cells survival rate and induce protein and mRNA expressions of p53; however, there is no consistency between the protein expression level of p53 and the mRNA expression level."
Wei Q, Luo Q, Liu H, Chen L, Cui H, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L - "The mitochondrial pathway is involved in sodium fluoride (NaF)-induced renal apoptosis in mice" Toxicol Res (Camb) 7(5):792-808 (2018) doi: 10.1039/c8tx00130h
https://academic.oup.com/toxres/article/7/5/792/5553450
"The mRNA expression levels of Cyt c, Bak, Bax, Bim, caspase-3 and p53 in the three NaF-treated groups at 21 days and 42 days of the experiment were all significantly higher (p < 0.01) than those in the control group."
Wen P, Wei X, Liang G, Wang Y, Yang Y, Qin L, Pang W, Qin G, Li H, Jiang Y, Wu Q - "Long-term exposure to low level of fluoride induces apoptosis via p53 pathway in lymphocytes of aluminum smelter workers" Environ Sci Pollut Res Int 26(3):2671-2680 (2019) doi: 10.1007/s11356-018-3726-z.
https://link.springer.com/article/10.10 ... 018-3726-z
"The expression levels of p53 and Bax were increased with fluoride exposure in lymphocytes (p < 0.05), whereas the Bcl-2 expression was decreased but not significantly. Taken together, these observations indicate that long-term occupational exposure to low level of fluoride may lead to oxidative stress and induce apoptosis through the p53-dependent pathway in peripheral blood lymphocytes of aluminum smelter workers. Serum fluoride level may be the potential biomarker of fluoride exposure."
Ying J, Xu J, Shen L, Mao Z, Liang J, Lin S, Yu X, Pan R, Yan C, Li S, Bao Q, Li P - "The Effect of Sodium Fluoride on Cell Apoptosis and the Mechanism of Human Lung BEAS-2B Cells In Vitro" Biol Trace Elem Res 179(1):59-69 (2017). doi: 10.1007/s12011-017-0937-y
https://link.springer.com/article/10.10 ... 017-0937-y
"The expressions of bax, caspase-3, caspase-9, p53, and the cytoplasmic CytC of the NaF groups increased, while bcl-2 and mitochondrial CytC decreased compared with that of the control group (P < 0.05)."
PFAS (only a few studies selected here)
Liu W, Yang B, Wu L, Zou W, Pan X, Zou T, Liu F, Xia L, Wang X, Zhang D - "Involvement of NRF2 in Perfluorooctanoic Acid-Induced Testicular Damage in Male Mice" Biol Reprod 93(2):41 (2015) doi: 10.1095/biolreprod.115.128819
https://academic.oup.com/biolreprod/art ... -7/2434244
"PFOA exposure up-regulated p-p53 and BAX expression and down-regulated BCL-2 expression in the testis."
Pierozan P, Kosnik M, Karlsson O - "High-content analysis shows synergistic effects of low perfluorooctanoic acid (PFOS) and perfluorooctane sulfonic acid (PFOA) mixture concentrations on human breast epithelial cell carcinogenesis" Environ Int 172:107746 (2023). doi: 10.1016/j.envint.2023.107746
https://www.sciencedirect.com/science/a ... 2023000193
Yang S, Liu S, Ren Z, Jiao X, Qin S - "Induction of oxidative stress and related transcriptional effects of perfluorononanoic acid using an in vivo assessment" Comp Biochem Physiol C Toxicol Pharmacol 160:60-5 (2014) doi: 10.1016/j.cbpc.2013.11.007
https://www.sciencedirect.com/science/a ... 5613001397
"The expression of p53, apoptosis-inducing factor (AIF) and c-Jun NH (2)-terminal kinase (JNK) was partially increased..."
Xie MY, Sun XF, Wu CC, Huang GL, Wang P, Lin ZY, Liu YW, Liu LY, Zeng EY - "Glioma is associated with exposure to legacy and alternative per- and polyfluoroalkyl substances" J Hazard Mater 441:129819 (2023) doi: 10.1016/j.jhazmat.2022.129819
https://www.sciencedirect.com/science/a ... 9422016120
"PFOA concentration positively correlated with glioma grade, Ki-67 and P53 expression."
Shi X, Du Y, Lam PK, Wu RS, Zhou B - " Developmental toxicity and alteration of gene expression in zebrafish embryos exposed to PFOS" Toxicol Appl Pharmacol 230(1):23-32 (2008) doi: 10.1016/j.taap.2008.01.043
https://www.sciencedirect.com/science/a ... 8X08000616
"Certain genes related to cell apoptosis, p53 and Bax, were both significantly up-regulated upon exposure to all the concentrations tested."
Xu D, Li L, Tang L, Guo M, Yang J - "Perfluorooctane sulfonate induces heart toxicity involving cardiac apoptosis and inflammation in rats" Exp Ther Med 23(1):14 (2022) doi: 10.3892/etm.2021.10936.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593915/
"The protein expressions profiles of p53 and Bax were also significantly upregulated in the 10 mg/kg PFOS group."
Zhang M, Bi X, Liu S, Liu Y, Wang Q - "The novel polyfluoroalkyl benzenesulfonate OBS exposure induces cell cycle arrest and senescence of rat pituitary cell GH3 via the p53/p21/RB pathway" Toxicology 490:153511 (2023) doi: 10.1016/j.tox.2023.153511
https://www.sciencedirect.com/science/a ... 3X23000975
"OBS notably activated the p53-p21 signalling pathway in GH3 cells, as evidenced by increased p53 and p21 expressions, enhanced p53 phosphorylation, and augmented p53 nuclear import."
Gq/11 (Only a few studies selected for the factors below, to show implications)
Wang Y, Xiao H, Wu H, Yao C, He H, Wang C, Li W - "G protein subunit α q regulates gastric cancer growth via the p53/p21 and MEK/ERK pathways" Oncol Rep 37(4):1998-2006 (2018). doi: 10.3892/or.2017.5500
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367349/
(Gastric cancer (GC) is the 4th most common cause of cancer-related deaths worldwide.)
Solyakov L, Sayan E, Riley J, Pointon A, Tobin AB - "Regulation of p53 expression, phosphorylation and subcellular localization by a G-protein-coupled receptor" Oncogene 28(41):3619-30 (2009). doi: 10.1038/onc.2009.225
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875175/
"In the current study we demonstrate that a classical Gq/11-coupled GPCR, the M3-muscarinic receptor, was able to regulate apoptosis via receptors that are endogenously expressed in the human neuroblastoma cell line SH-SY5Y and when ectopically expressed in Chinese hamster ovary (CHO) cells. Stimulation of the M3-muscarinic receptor was shown to inhibit the ability of the DNA-damaging chemotherapeutic agent, etoposide, from mediating apoptosis. This protective response in CHO cells correlated with the ability of the receptor to regulate the expression levels of p53."
D2
Nappi A, Miro C, Pezone A, Tramontano A, Di Cicco E, Sagliocchi S, Cicatiello AG, Murolo M, Torabinejad S, Abbotto E, Caiazzo G, Raia M, Stornaiuolo M, Antonini D, Fabbrocini G, Salvatore D, Avvedimento VE, Dentice M - "Loss of p53 activates thyroid hormone via type 2 deiodinase and enhances DNA damage" Nat Commun 14(1):1244 (2023) doi: 10.1038/s41467-023-36755-y
https://www.nature.com/articles/s41467-023-36755-y
"Here, we show that the cell stress sensor and tumor suppressor p53 silences D2 expression, thereby lowering the intracellular THs availability."
Nappi A, Miro C, Pezone A, Tramontano A, Di Cicco E, Sagliocchi S, Cicatiello AG, Murolo M, Torabinejad S, Abbotto E, Caiazzo G, Raia M, Stornaiuolo M, Antonini D, Fabbrocini G, Salvatore D, Avvedimento VE, Dentice M - "Loss of p53 activates thyroid hormone via type 2 deiodinase and enhances DNA damage" Nat Commun 14(1):1244 (2023) doi: 10.1038/s41467-023-36755-y
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9985592/
"In vivo genetic deletion of D2 significantly reduces cancer progression and suggests that targeting THs may represent a general tool reducing invasiveness in p53-mutated neoplasms."
Thyroid Status
Wei X, Tan J, Gao H - "Role of sirtuin 1 in the brain development in congenital hypothyroidism rats via the regulation of p53 signaling pathway" Bioengineered 13(4):9455-9466 (2022) doi: 10.1080/21655979.2022.2060626
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161855/
Qi JS, Yuan Y, Desai-Yajnik V, Samuels HH -"Regulation of the mdm2 oncogene by thyroid hormone receptor" Mol Cell Biol 19(1):864-72(1999)
"We report that thyroid hormone (T3) receptors (T3Rs)... regulate mdm2 through the same intron sequences that are modulated by p53."
SEE: SIRT1