The exposure of living organisms to environmental stress triggers defensive responses resulting in the activation of protective processes. Whenever the exposure occurs at low doses, defensive effects overwhelm the adverse effects of the exposure; this adaptive situation is referred to as "hormesis". Environmental, physical, and nutritional hormetins lead to the stimulation and strengthening of the maintenance and repair systems in cells and tissues. Exercise, heat, and irradiation are examples of physical hormetins, which activate heat shock-, DNA repair-, and anti-oxidative-stress responses. The health promoting effect of many bio-actives in fruits and vegetables can be seen as the effect of mildly toxic compounds triggering this adaptive stimulus. Numerous studies indicate that living organisms possess the ability to adapt to adverse environmental conditions, as exemplified by the fact that DNA damage and gene expression profiling in populations living in the environment with high levels of air pollution do not correspond to the concentrations of pollutants. The molecular mechanisms of the hormetic response include modulation of (a) transcription factor Nrf2 activating the synthesis of glutathione and the subsequent protection of the cell; (b) DNA methylation; and (c) microRNA. These findings provide evidence that hormesis is a toxicological event, occurring at low exposure doses to environmental stressors, having the benefit for the maintenance of a healthy status.

Campus Venlo Maastricht University 5900 AA Venlo The Netherlands

Department of Experimental Medicine University of Genoa 16132 Genoa Italy

Department of Genetic Toxicology and Epigenetics Institute of Experimental Medicine 14220 Prague Czech Republic

Department of Health Science University of Genoa 16132 Genoa Italy

Department of Molecular Biology and Genetics Aarhus University 8000 Aarhus Denmark

Department of Nanotoxicology and Molecular Epidemiology Institute of Experimental Medicine 14220 Prague Czech Republic

Department of Pharmacology and Toxicology Maastricht University 6200 MD Maastricht The Netherlands

IRCCS Ospedale Policlinico San Martino 16132 Genoa Italy

See more in PubMed

Levine J.A., Kotz C.M. NEAT-Non-exercise activity thermogenesis-egocentric & geocentric environmental factors vs. biological regulation. Acta Physiol. Scand. 2005;184:309–318. PubMed

Rodriguez-Mateos A., Vauzour D., Krueger C.G., Shanmuganayagam D., Reed J., Calani L., Mena P., Del Rio D., Crozier A. Bioavailability, bioactivity and impact on health of dietary flavonoids and related compounds: An update. Arch. Toxicol. 2014;88:1803–1853. doi: 10.1007/s00204-014-1330-7. PubMed DOI

Calabrese V., Scapagnini G., Stella A.M.G., Bates T., Clark J.B. Mitochondrial Involvement in Brain Function and Dysfunction: Relevance to Aging, Neurodegenerative Disorders and Longevity. Neurochem. Res. 2001;26:739–764. doi: 10.1023/a:1010955807739. PubMed DOI

Benayoun B.A., Pollina E.A., Brunet A. Epigenetic regulation of ageing: Linking environmental inputs to genomic stability. Nat. Rev. Mol. Cell Biol. 2015;16:593–610. doi: 10.1038/nrm4048. PubMed DOI PMC

Hu Z., Brooks S.A., Dormoy V., Hsu C.-W., Hsu H.-Y., Lin L.-T., Massfelder T., Rathmell W.K., Xia M., Al-Mulla F., et al. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: Focus on the cancer hallmark of tumor angiogenesis. Carcinogenesis. 2015;36:S184–S202. doi: 10.1093/carcin/bgv036. PubMed DOI PMC

Izzotti A., Pulliero A. The effects of environmental chemical carcinogens on the microRNA machinery. Int. J. Hyg. Environ. Health. 2014;217:601–627. doi: 10.1016/j.ijheh.2014.01.001. PubMed DOI

Izzotti A., Balansky R., Cartiglia C., Camoirano A., Longobardi M., De Flora S. Genomic and transcriptional alterations in mouse fetus liver after transplacental exposure to cigarette smoke. FASEB J. 2003;17:1127–1129. doi: 10.1096/fj.02-0967fje. PubMed DOI

Izzotti A., Balansky R.M., Camoirano A., Cartiglia C., Longobardi M., Tampa E., De Flora S. Birth-related genomic and transcripional changes in mouse lung. Modulation by transplacental N-acetylcysteine. Mutat. Res. (Rev. Mutat. Res.) 2003;544:441–449. PubMed

Izzotti A., Calin G.A., Steele V.E., Croce C.M., De Flora S. Relationships of microRNA expression in mouse lung with age and exposure to cigarette smoke and light. FASEB J. 2009;23:3243–3250. doi: 10.1096/fj.09-135251. PubMed DOI PMC

Izzotti A., Cartiglia C., Tanningher M., De Flora S., Balansky R. Age-related increases of 8-hydroxy-2′-deoxyguanosine and DNA protein cross-link in mouse organs. Mutat. Res. Genet. Toxicol. Environ. Mutat. 1999;446:215–223. PubMed

Mifsud K.R., Gutièrrez-Mecinas M., Trollope A.F., Collins A., Saunderson E.A., Reul J.M. Epigenetic mechanisms in stress and adaptation. Brain Behav. Immun. 2011;25:1305–1315. doi: 10.1016/j.bbi.2011.06.005. PubMed DOI

Calabrese E.J., Bachmann K.A., Baileru A.J., Bolger P.M., Borak J., Cai L., Cedergreen N., Cherian M.G., Chiueh C.C., Clarkson T.W., et al. Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose–response framework. Toxicol. Appl. Pharmacol. 2007;222:122–128. doi: 10.1016/j.taap.2007.02.015. PubMed DOI

Wogan G.N. Molecular epidemiology in cancer risk assessment and prevention: Recent progress and avenues for future research. Environ. Health Perspect. 1992;98:167–178. doi: 10.1289/ehp.9298167. PubMed DOI PMC

Xue M., Rabbani N., Momiji H., Imbasi P., Anwar M.M., Kitteringham N., Park B.K., Souma T., Moriguchi T., Yamamoto M., et al. Transcriptional control of glyoxalase 1 by Nrf2 provides a stress-responsive defence against dicarbonyl glycation. Biochem. J. 2012;443:213–222. doi: 10.1042/BJ20111648. PubMed DOI

Dubrova Y.E. Nuclear Weapons Tests and Human Germline Mutation Rate. Science. 2002;295:1037. doi: 10.1126/science.1068102. PubMed DOI

König D., Neubauer O., Nics L., Kern N., Berg A., Bisse E., Wagner K.-H. Biomarkers of exercise-induced myocardial stress in relation to inflammatory and oxidative stress. Exerc. Immunol. Rev. 2007;13:15–36. PubMed

Rattan S.I.S. Hormesis in aging. Ageing Res. Rev. 2008;7:63–78. doi: 10.1016/j.arr.2007.03.002. PubMed DOI

Bhattacharya S., Rattan S.I.S. Primary stress response pathways for pre-conditioning and physiological hormesis. In: Rattan S., Kyriazis M., editors. The Science of Hormesis in Health and Longevity. Academic Press; Cambridge, MA, USA: 2019. pp. 35–54. Chapter 3.

Calabrese V., Cornelius C., Cuzzocrea S., Iavicoli I., Rizzarelli E., Calabrese E.J. Hormesis, cellular stress response and vitagenes as critical determinants in aging and longevity. Mol. Asp. Med. 2011;32:279–304. doi: 10.1016/j.mam.2011.10.007. PubMed DOI

Calabrese E.J., Mattson M.P. Hormesis provides a generalized quantitative estimate of biological plasticity. J. Cell Commun. Signal. 2011;5:25–38. doi: 10.1007/s12079-011-0119-1. PubMed DOI PMC

Calabrese V., Cornelius C., Trovato A., Cambria M.T., Locascio M., Rienzo L., Condorelli D.F., Mancuso C., De Lorenzo A., Calabrese E. The Hormetic Role of Dietary Antioxidants in Free Radical-Related Diseases. Curr. Pharm. Des. 2010;16:877–883. doi: 10.2174/138161210790883615. PubMed DOI

Callahan D. WHO definition of “health”. Stud. Hastings Cent. 1973;1:77–88. doi: 10.2307/3527467. PubMed DOI

Saulnier D.D., Hean H., Thol D., Ir P., Hanson C., Von Schreeb J., Alvesson H.M. Staying afloat: Community perspectives on health system resilience in the management of pregnancy and childbirth care during floods in Cambodia. BMJ Glob. Health. 2020;5:e002272. doi: 10.1136/bmjgh-2019-002272. PubMed DOI PMC

Surh Y.-J. Cancer chemoprevention with dietary phytochemicals. Nat. Rev. Cancer. 2003;3:768–780. doi: 10.1038/nrc1189. PubMed DOI

Rogan E.G. The natural chemopreventive compound indole-3-carbinol: State of the science. In Vivo. 2006;20:221–228. PubMed

Akhlaghi M., Bandy B., Akhlaghi M. Dietary green tea extract increases phase 2 enzyme activities in protecting against myocardial ischemia-reperfusion. Nutr. Res. 2010;30:32–39. doi: 10.1016/j.nutres.2009.11.002. PubMed DOI

Calabrese E.J., Shamoun D.Y., Hanekamp J.C. Cancer risk assessment: Optimizing human health through linear dose–response models. Food Chem. Toxicol. 2015;81:137–140. doi: 10.1016/j.fct.2015.04.023. PubMed DOI

Tirumalai R., Kumar T.R., Mai K.H., Biswal S. Acrolein causes transcriptional induction of phase II genes by activation of Nrf2 in human lung type II epithelial (A549) cells. Toxicol. Lett. 2002;132:27–36. doi: 10.1016/S0378-4274(02)00055-3. PubMed DOI

Pocernich C.B., Cardin A.L., Racine C.L., Lauderback C.M., Butterfield D.A. Glutathione elevation and its protective role in acrolein-induced protein damage in synaptosomal membranes: Relevance to brain lipid peroxidation in neurodegenerative disease. Neurochem. Int. 2001;39:141–149. doi: 10.1016/S0197-0186(01)00012-2. PubMed DOI

Sun X., Yang Y., Shi J., Wang C., Yu Z., Zhang H. NOX4- and Nrf2-mediated oxidative stress induced by silver nanoparticles in vascular endothelial cells. J. Appl. Toxicol. 2017;37:1428–1437. doi: 10.1002/jat.3511. PubMed DOI

Vargas-Mendoza N., Morales-González Á., Madrigal-Santillán E., Madrigal-Bujaidar E., Álvarez-González I., García-Melo L.F., Anguiano-Robledo L., Fregoso-Aguilar T., Morales-González J. Antioxidant and Adaptative Response Mediated by Nrf2 during Physical Exercise. Antioxidants. 2019;8:196. doi: 10.3390/antiox8060196. PubMed DOI PMC

Izzotti A., Balansky R.M., Dagostini F., Bennicelli C., Myers S.R., Grubbs C.J., Lubet R., Kelloff G.J., De Flora S. Modulation of biomarkers by chemopreventive agents in smoke-exposed rats. Cancer Res. 2001;61:2472–2479. PubMed

Izzotti A., Cartiglia C., Steele V.E., De Flora S. MicroRNAs as targets for dietary and pharmacological inhibitors of mutagenesis and carcinogenesis. Mutat. Res. Mol. Mech. Mutagen. 2012;751:287–303. doi: 10.1016/j.mrrev.2012.05.004. PubMed DOI PMC

Anway M.D., Cupp A.S., Uzumcu M., Skinner M.K. Epigenetic Transgenerational Actions of Endocrine Disruptors and Male Fertility. Science. 2005;308:1466–1469. doi: 10.1126/science.1108190. PubMed DOI PMC

Gómez-Schiavon M., Buchler N.E. Epigenetic switching as a strategy for quick adaptation while attenuating biochemical noise. PLoS Comput. Biol. 2019;15:e1007364. doi: 10.1371/journal.pcbi.1007364. PubMed DOI PMC

Barnthouse L.W., Glaser D., DeSantis L. Polychlorinated bisphenyls and Hudson River white perch: Implications for population-level ecological risk assessment and risk management. Integr. Environ. Assess. Manag. 2009;5:435–444. doi: 10.1897/IEAM_2008-080.1. PubMed DOI

Wirgin I., Roy N.K., Loftus M., Chambers R.C., Franks D.G., Hahn M.E. Mechanistic Basis of Resistance to PCBs in Atlantic Tomcod from the Hudson River. Science. 2011;331:1322–1325. doi: 10.1126/science.1197296. PubMed DOI PMC

Natarajan A.T., Boei J.J., Darroudi F., Van Diemen P.C., Dulout F., Hande M.P., Ramalho A.T. Current cytogenetic methods for detecting exposure and effects of mutagens and carcinogens. Environ. Health Perspect. 1996;104:445–448. PubMed PMC

Dulout F.N., Grillo C.A., Seoane A.I., Maderna C.R., Nilsson R., Vahter M., Darroudi F., Natarajan A.T. Chromosomal aberrations in peripheral blood lymphocytes from native Andrean women and children from northwestern Argentina exposed to arsenic in drinking water. Mutat. Res. 1996;370:151–158. doi: 10.1016/S0165-1218(96)00060-2. PubMed DOI

Vahter M., Concha G., Nermell B., Nilsson R., Dulout F., Natarajan A.T. A unique metabolism of inorganic arsenic in native Andean women. Eur. J. Pharmacol. 1995;293:455–466. doi: 10.1016/0926-6917(95)90066-7. PubMed DOI

Schlebusch C.M., Gattepaille L., Vahter M., Jakobsson M., Broberg K., Engström K. Human Adaptation to Arsenic-Rich Environments. Mol. Biol. Evol. 2015;32:1544–1555. doi: 10.1093/molbev/msv046. PubMed DOI

Rossnerova A., Pokorna M., Svecova V., Šrám R.J., Topinka J., Zolzer C.S.F., Rossner P. Adaptation of the human population to the environment: Current knowledge, clues from Czech cytogenetic and “omics” biomonitoring studies and possible mechanisms. Mutat. Res. Mutat. Res. 2017;773:188–203. doi: 10.1016/j.mrrev.2017.07.002. PubMed DOI

Rossner P., Jr., Svecova V., Schmuczerova J., Milcova A., Tabashidze N., Topinka J., Pastorkova A., Sram R.J. Analysis of biomarkers in a Czech population exposed to heavy air pollution. Part I: Bulky DNA adducts. Mutagenesis. 2013;28:89–95. doi: 10.1093/mutage/ges057. PubMed DOI

Rossner P., Jr., Rossnerova A., Spatova M., Beskid O., Uhlirova K., Libalova H., Solansky I., Topinka J., Sram R.J. Analysis of biomarkers in a Czech population exposed to heavy air pollution. Part II: Chromosomal aberrations and oxidative stress. Mutagenesis. 2013;28:97–106. doi: 10.1093/mutage/ges058. PubMed DOI

Rossnerova A., Spatova M., Schunck C., Šrám R.J. Automated scoring of lymphocyte micronuclei by the MetaSystems Metafer image cytometry system and its application in studies of human mutagen sensitivity and biodosimetry of genotoxin exposure. Mutagenesis. 2010;26:169–175. doi: 10.1093/mutage/geq057. PubMed DOI

Rossner P., Uhlirova K., Beskid O., Rossnerova A., Svecova V., Šrám R.J. Expression of XRCC5 in peripheral blood lymphocytes is upregulated in subjects from a heavily polluted region in the Czech Republic. Mutat. Res. Mol. Mech. Mutagen. 2011;713:76–82. doi: 10.1016/j.mrfmmm.2011.06.001. PubMed DOI

Rossner P., Tulupova E., Rossnerova A., Libalova H., Honkova K., Gmuender H., Pastorkova A., Svecova V., Topinka J., Šrám R.J. Reduced gene expression levels after chronic exposure to high concentrations of air pollutants. Mutat. Res. Mol. Mech. Mutagen. 2015;780:60–70. doi: 10.1016/j.mrfmmm.2015.08.001. PubMed DOI

Rossnerova A., Tulupova E., Tabashidze N., Schmuczerova J., Dostal M., Rossner P., Gmuender H., Šrám R.J. Factors affecting the 27K DNA methylation pattern in asthmatic and healthy children from locations with various environments. Mutat. Res. Mol. Mech. Mutagen. 2013;741:18–26. doi: 10.1016/j.mrfmmm.2013.02.003. PubMed DOI

Rider C.F., Carlsten C. Air pollution and DNA methylation: Effects of exposure in humans. Clin. Epigenet. 2019;11:131. doi: 10.1186/s13148-019-0713-2. PubMed DOI PMC

Ferrari L., Carugno M., Bollati V. Particulate matter exposure shapes DNA methylation through the lifespan. Clin. Epigenet. 2019;11:129. doi: 10.1186/s13148-019-0726-x. PubMed DOI PMC

Plusquin M., Guida F., Polidoro S., Vermeulen R., Raaschou-Nielsen O., Campanella G., Hoek G., Kyrtopoulos S.A., Georgiadis P., Naccarati A., et al. DNA methylation and exposure to ambient air pollution in two perspective cohorts. Environ. Int. 2017;108:127–136. doi: 10.1016/j.envint.2017.08.006. PubMed DOI PMC

Rossnerova A., Pelclova D., Zdimal V., Rossner P., Jr., Elzeinova F., Vrbova K., Topinka J., Schwarz J., Ondracek J., Kostejn M., et al. Micronucleus levels in nanocomposites production workers: Interpretation of results from two years of monitoring; Proceedings of the NANOCON: 10th Anniversary International Conference on Nanomaterials—Research & Application; Brno, Czech Republic. 17–19 October 2018; pp. 554–559.

Rossnerova A., Pelclova D., Zdimal V., Rossner P., Elzeinova F., Vrbova K., Topinka J., Schwarz J., Ondracek J., Kostejn M., et al. The repeated cytogenetic analysis of subjects occupationally exposed to nanoparticles: A pilot study. Mutagensis. 2019;34:253–263. doi: 10.1093/mutage/gez016. PubMed DOI

Rossnerova A., Honkova K., Pelclova D., Ždímal V., Hubáček J.A., Chvojkova I., Vrbova K., Rossner P., Topinka J., Vlckova S., et al. DNA Methylation Profiles in a Group of Workers Occupationally Exposed to Nanoparticles. Int. J. Mol. Sci. 2020;21:2420. doi: 10.3390/ijms21072420. PubMed DOI PMC

Zhou J., Jenkins T.G., Jung A.M., Jeong K.S., Zhai J., Jacobs E.T., Griffin S.C., Dearmon-Moore D., Littau S.R., Peate W.F., et al. DNA methylation among firefighters. PLoS ONE. 2019;14:e0214282. doi: 10.1371/journal.pone.0214282. PubMed DOI PMC

Van Der Plaat D.A., De Jong K., De Vries M., Van Diemen C.C., Nedeljkovic I., Amin N., Kromhout H., Vermeulen R.C.H., Postma D.S., Van Duijn C.M., et al. Occupational exposure to pesticides is associated with differential DNA methylation. Occup. Environ. Med. 2018;75:427–435. doi: 10.1136/oemed-2017-104787. PubMed DOI PMC

Yu X., Zhao B., Su Y., Zhang Y., Chen J., Wu W., Cheng Q., Guo X., Zhao Z., Ke X., et al. Association of prenatal organochlorine pesticide-dichlorodiphenyltrichloroethane exposure with fetal genome-wide DNA methylation. Life Sci. 2018;200:81–86. doi: 10.1016/j.lfs.2018.03.030. PubMed DOI

Zeng Z., Huo X., Zhang Y., Hylkema M.N., Wu Y., Xu X. Differential DNA methylation in newborns with maternal exposure to heavy metals from an e-waste recycling area. Environ. Res. 2019;171:536–545. doi: 10.1016/j.envres.2019.01.007. PubMed DOI

Chung F.F.-L., Herceg Z. The Promises and Challenges of Toxico-Epigenomics: Environmental Chemicals and Their Impacts on the Epigenome. Environ. Health Perspect. 2020;128:15001. doi: 10.1289/EHP6104. PubMed DOI PMC

Heijmans B.T., Tobi E.W., Stein A.D., Putter H., Blauw G.J., Susser E.S., Slagboom E.P., Lumey L.H. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc. Natl. Acad. Sci. USA. 2008;105:17046–17049. doi: 10.1073/pnas.0806560105. PubMed DOI PMC

Laufer B.I., Kapalanga J., Castellani C.A., Chater-Diehl E.J., Yan L., Singh S.M. Associative DNA methylation changes in children with prenatal alcohol exposure. Epigenomics. 2015;7:1259–1274. doi: 10.2217/epi.15.60. PubMed DOI

Markunas C.A., Xu Z., Harlid S., Wade P.A., Lie R.T., Taylor J.A., Wilcox A.J. Identification of DNA Methylation Changes in Newborns Related to Maternal Smoking during Pregnancy. Environ. Health Perspect. 2014;122:1147–1153. doi: 10.1289/ehp.1307892. PubMed DOI PMC

Wilson R., Wahl S., Pfeiffer L., Ward-Caviness C.K., Kunze S., Kretschmer A., Reischl E., Peters A., Gieger C., Waldenberger M. The dynamics of smoking-related disturbed methylation: A two time-point study of methylation change in smokers, non-smokers and former smokers. BMC Genom. 2017;18:805. doi: 10.1186/s12864-017-4198-0. PubMed DOI PMC

DiMauro I., Paronetto M.P., Caporossi D. Exercise, redox homeostasis and the epigenetic landscape. Redox Biol. 2020;35:101477. doi: 10.1016/j.redox.2020.101477. PubMed DOI PMC

Bateson P., Gluckman P., Hanson M.A. The biology of developmental plasticity and the Predictive Adaptive Response hypothesis. J. Physiol. 2014;592:2357–2368. doi: 10.1113/jphysiol.2014.271460. PubMed DOI PMC

Bird A.P. DNA methylation patterns and epigenetic memory. Genes Dev. 2002;16:6–21. doi: 10.1101/gad.947102. PubMed DOI

D’Urso A., Brickner J.H. Mechanisms of epigenetic memory. Trends Genet. 2014;30:230–236. doi: 10.1016/j.tig.2014.04.004. PubMed DOI PMC

Kim K., Doi A., Wen B., Ng K., Zhao R., Cahan P., Kim J., Aryee M.J., Ji H., Ehrlich L.I.R., et al. Epigenetic memory in induced pluripotent stem cells. Nature. 2010;467:285–290. doi: 10.1038/nature09342. PubMed DOI PMC

Sen A., Cingolani P., Senut M.-C., Land S., Mercado-García A., Téllez-Rojo M.M., Baccarelli A., Wright R., Ruden D.M. Lead exposure induces changes in 5-hydroxymethylcytosine clusters in CpG islands in human embryonic stem cells and umbilical cord blood. Epigenetics. 2015;10:607–621. doi: 10.1080/15592294.2015.1050172. PubMed DOI PMC

Danielsson A., Barreau K., Kling T., Tisell M., Carén H. Accumulation of DNA methylation alterations in paediatric glioma stem cells following fractionated dose irradiation. Clin. Epigenet. 2020;12:1–13. doi: 10.1186/s13148-020-0817-8. PubMed DOI PMC

Vineis P., Chatziioannou A., Cunliffe V.T., Flanagan J.M., Hanson M., Kirsch-Volders M., Kyrtopoulos S. Epigenetic memory in response to environmental stressors. FASEB J. 2017;31:2241–2251. doi: 10.1096/fj.201601059RR. PubMed DOI

Kuzmina N.S., Lapteva N.S., Rusinova G.G., Azizova T.V., Vyazovskava N.S., Rubanovich A.V. Gene hypermethylation in blood leukocytes in humans long term after radiation exposure—Validation set. Environ. Pollut. 2018;234:935–942. doi: 10.1016/j.envpol.2017.12.039. PubMed DOI

Henschel S., Atkinson R., Zeka A., Le Tertre A., Analitis A., Katsouyanni K., Chanel O., Pascal M., Forsberg B., Medina S., et al. Air pollution interventions and their impact on public health. Int. J. Public Health. 2012;57:757–768. doi: 10.1007/s00038-012-0369-6. PubMed DOI

Šrám R.J., Binkova B., Dostal M., Merkerova M.D., Libalova H., Milcova A., Rossner P., Rossnerova A., Schmuczerova J., Svecova V., et al. Health impact of air pollution to children. Int. J. Hyg. Environ. Health. 2013;216:533–540. doi: 10.1016/j.ijheh.2012.12.001. PubMed DOI

Alias C., Benassi L., Bertazzi L., Sorlini S., Volta M., Gelatti U. Environmental exposure and health effects in a highly polluted area of Northern Italy: A narrative review. Environ. Sci. Pollut. Res. 2019;26:4555–4569. doi: 10.1007/s11356-018-4040-5. PubMed DOI

Ma Y., He X., Qi K., Wang T., Qi Y., Cui L., Wang F., Song M. Effects of environmental contaminants on fertility and reproductive health. J. Environ. Sci. 2019;77:210–217. doi: 10.1016/j.jes.2018.07.015. PubMed DOI

Šrám R.J., Binková B., Rössner P., Rubeš J., Topinka J., Dejmek J. Adverse reproductive outcomes from exposure to environmental mutagens. Mutat. Res. Mol. Mech. Mutagen. 1999;428:203–215. doi: 10.1016/S1383-5742(99)00048-4. PubMed DOI

Vaiserman A.M. Hormesis and epigenetics: Is there a link? Ageing Res. Rev. 2011;10:413–421. doi: 10.1016/j.arr.2011.01.004. PubMed DOI

Vandegehuchte M.B., Janssen C.R. Epigenetics in an ecotoxicological context. Mutat. Res. Toxicol. Environ. Mutagen. 2014;764:36–45. doi: 10.1016/j.mrgentox.2013.08.008. PubMed DOI

Mirbahai L., Chipman J.K. Epigenetic memory of environmental organisms: A reflection of lifetime stressor exposures. Mutat. Res. Toxicol. Environ. Mutagen. 2014;764:10–17. doi: 10.1016/j.mrgentox.2013.10.003. PubMed DOI

Giuliani C., Bacalini M.G., Sazzini M., Pirazzini C., Franceschi C., Garagnani P., Luiselli D. The epigenetic side of human adaptation: Hypotheses, evidences and theories. Ann. Hum. Biol. 2014;42:1–9. doi: 10.3109/03014460.2014.961960. PubMed DOI

Agathokleous E., Kitao M., Calabrese E.J. Environmental hormesis and its fundamental biological basis: Rewriting the history of toxicology. Environ. Res. 2018;165:274–278. doi: 10.1016/j.envres.2018.04.034. PubMed DOI

Izzotti A., Calin G.A., Arrigo P., Steele V.E., Croce C.M., De Flora S. Downregulation of microRNA expression in the lungs of rats exposed to cigarette smoke. FASEB J. 2009;23:806–812. doi: 10.1096/fj.08-121384. PubMed DOI PMC

Izzotti A., Bagnasco M., Cartiglia C., Longobardi M., De Flora S. Proteomic analysis as related to transcriptome data in the lung of chromium(VI)-treated rats. Int. J. Oncol. 2004;24:1513–1522. PubMed

Ligorio M., Izzotti A., Pulliero A., Arrigo P. Mutagens interfere with microRNA maturation by inhibiting DICER. An in silico biology analysis. Mutat. Res. 2011;717:116–128. doi: 10.1016/j.mrfmmm.2011.07.020. PubMed DOI

Kaina B., Izzotti A., Xu J.-Z., Christmann M., Pulliero A., Zhao X., Dobreanu M., Au W.W. Inherent and toxicant-provoked reduction in DNA repair capacity: A key mechanism for personalized risk assessment, cancer prevention and intervention, and response to therapy. Int. J. Hyg. Environ. Health. 2018;221:993–1006. doi: 10.1016/j.ijheh.2018.07.003. PubMed DOI

Genome-Wide DNA Methylation in Policemen Working in Cities Differing by Major Sources of Air Pollution

Individual DNA Methylation Pattern Shifts in Nanoparticles-Exposed Workers Analyzed in Four Consecutive Years

The Impact of Air Pollution Exposure on the MicroRNA Machinery and Lung Cancer Development