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Hormesis provides a generalized quantitative estimate of biological plasticity

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Abstract

Phenotypic plasticity represents an environmentally-based change in an organism’s observable properties. Since biological plasticity is a fundamental adaptive feature, it has been extensively assessed with respect to its quantitative features and genetic foundations, especially within an ecological evolutionary framework. Toxicological investigations on the dose-response continuum (i.e., very broad dose range) that include documented evidence of the hormetic dose response zone (i.e., responses to doses below the toxicological threshold) can be employed to provide a quantitative estimate of phenotypic plasticity. The low dose hormetic stimulation is an adaptive response that reflects an environmentally-induced altered phenotype and provides a quantitative estimate of biological plasticity. Analysis of nearly 8,000 dose responses within the hormesis database indicates that quantitative features of phenotypic plasticity are highly generalizable, being independent of biological model, endpoint measured and chemical/physical stress inducing agent. The magnitude of phenotype changes indicative of plasticity is modest with maximum responses typically being approximately 30–60% greater than control values. The present findings provide the first quantitative estimates of biological plasticity and its capacity for generalization. Summary This article provides the first quantitative estimate of biological plasticity that may be generalized across plant, microbial, animal systems, and across all levels of biological organization. The quantitative features of plasticity are described by the hormesis dose response model. These findings have important biological, biomedical and evolutionary implications.

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References

  • Agrawal AA (2000) Overcompensation of plants in response to herbivory and the by-product benefits of mutualism. Trends Plant Sci 5:309–313

    Article  CAS  PubMed  Google Scholar 

  • Begley S (2007) Train Your Brain, Change Your Mind. Balantine Books, pp 304

  • Bierzychudek P (1989) Environment sensitivity of sexual and apomictic Antennaria: Do apomicts have general-purpose genotypes? Evolution 43:1456–1466

    Article  Google Scholar 

  • Bradshaw AD (1965) Evolutionary significance of phenotypic plasticity in plants. Adv Genet 13:115–155

    Article  Google Scholar 

  • Bull JJ (1987) Evolution of phenotypic variance. Evolution 41:303–315

    Article  Google Scholar 

  • Calabrese EJ (2001) Overcompensation stimulation: A mechanism for hormetic effects. Crit Rev Toxicol 31:425–470

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2005a) Paradigm lost, paradigm found: The re-emergence of hormesis as a fundamental dose response model in the toxicological sciences. Env Poll 138:378–411

    Article  CAS  Google Scholar 

  • Calabrese EJ (2005b) Cancer biology and hormesis: human tumor cell lines commonly display hormetic (biphasic) dose responses. Crit Rev Toxicol 35:463–582

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2005c) Hormetic dose-response relationships in immunology: Occurrence, quantitative features of the dose response, mechanistic foundations, and clinical implications. Crit Rev Toxicol 35:89–296

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2008a) Hormesis: Why it is important to toxicology and toxicologists. Env Toxicol Chem 27:1451–1474

    Article  CAS  Google Scholar 

  • Calabrese EJ (2008b) Converging concepts: adaptive response, preconditioning, and the Yerkes-Dodson law are manifestations of hormesis. Aging Res Rev 7:8–20

    Article  CAS  Google Scholar 

  • Calabrese EJ (2008c) Stress biology and hormesis: The Yerkes-Dodson law in psychology—a special case of the hormesis dose response. Crit Rev Toxicol 38:453–462

    Article  PubMed  Google Scholar 

  • Calabrese EJ (2008d) Alzheimer’s disease drugs: An application of the hormetic dose-response model. Crit Rev Toxicol 38:419–451

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2008e) Pharmacological enhancement of neuronal survival. Crit Rev Toxicol 38:349–389

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2008f) Enhancing and regulating neurite outgrowth. Crit Rev Toxicol 38:391–418

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2008g) Modulation of the epileptic seizure threshold: Implications of biphasic dose responses. Crit Rev Toxicol 38:543–556

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2008h) An assessment of anxiolytic drug screening tests: Hormetic dose responses predominate. Crit Rev Toxicol 38:489–542

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2008i) Pain and U-shaped dose responses: Occurrence, mechanisms, and clinical implications. Crit Rev Toxicol 38:579–590

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2010) Hormesis is central to toxicology, pharmacology and risk assessment. Hum Exper Toxicol 29:249–261

    Article  Google Scholar 

  • Calabrese EJ, Baldwin L (1997) The dose determines the stimulation (and poison): Development of a chemical hormesis data base. Int J Toxicol 16:545–559

    Article  CAS  Google Scholar 

  • Calabrese EJ, Baldwin LA (2001) The frequency of U-shaped dose-responses in the toxicological literature. Tox Sci 62:330–338

    Article  CAS  Google Scholar 

  • Calabrese EJ, Baldwin LA (2002) Defining Hormesis. Hum Exper Toxicol 21:91–97

    Article  CAS  Google Scholar 

  • Calabrese EJ, Baldwin LA (2003) The hormetic dose response model is more common than the threshold model in toxicology. Tox Sci 71:246–250

    Article  CAS  Google Scholar 

  • Calabrese EJ, Blain R (2005) The occurrence of hormetic dose responses in the toxicological literature, the hormesis database: An overview. Toxicol Appl Pharmacol 202:289–301

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ, Blain RB (2009) Hormesis and plant biology. Environ Poll 157:42–48

    Article  CAS  Google Scholar 

  • Calabrese EJ, Staudenmayer JW, Stanek EJ, Hoffmann GR (2006) Hormesis outperforms threshold model in NCI anti-tumor drug screening data. Tox Sci 94:368–378

    Article  CAS  Google Scholar 

  • Calabrese EJ et al (2007) Biological stress terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework. Tox Appl Pharmacol 222:122–128

    Article  CAS  Google Scholar 

  • Calabrese EJ, Stanek EJ III, Nascarella MA, Hoffmann GR (2008) Hormesis predicts low-dose responses better than threshold models. Int J Toxicol 27:369–378

    Article  CAS  PubMed  Google Scholar 

  • De Jong G (1995) Phenotypic plasticity as a product of selection in a variable environment. Amer Nat 145:493–512

    Article  Google Scholar 

  • Falconer DS (1990) Selection in different environments: effects on environmental sensitivity (reaction norm) and on mean performance. Genet Res Camb 56:57–70

    Article  Google Scholar 

  • Flood JF, Smith GE, Cherkin A (1982) Memory retention—Enhancement by cholinergic drug-combinations in mice. Gerontol 22:230–231

    Google Scholar 

  • Flood JF, Smith GE, Cherkin A (1983) Memory retention—Potentiation of cholinergic drug-combinations in mice. Neurobiol Aging 4:37–43

    Article  CAS  PubMed  Google Scholar 

  • Flood JF, Smith GE, Cherkin A (1984) Memory retention—Enhancement by synergistic oral cholinergic drug-combination in mice. Gerontol 24:149

    Google Scholar 

  • Flood JF, Smith GE, Cherkin A (1985) Memory enhancement—Supra-additive effect of subcutaneous chlolinergic drug-combinations in mice. Psychopharmacology 86:61–67

    Article  CAS  PubMed  Google Scholar 

  • Freeman GH (1973) Statistical methods for the analysis of genotype-environment interactions. Heredity 31:339–354

    Article  CAS  PubMed  Google Scholar 

  • Gomulkiewic R, Kirkpatrick M (1992) Quantitative genetics and the evolution of reaction norms. Evolution 46:390–411

    Article  Google Scholar 

  • Huey RB, Kingsolver JG (1989) Evolution of thermal sensitivity of ectotherm performance. Trends Ecol Evol 4:131–135

    Article  CAS  PubMed  Google Scholar 

  • Izem R, Kingsolver JG (2005) Variation in continuous reaction norms: Quantifying directions of biological interest. Amer Nat 166:276–289

    Google Scholar 

  • Jinks JL, Pooni HS (1988) The genetic basis of environmental sensitivity. In: Weir BS, Eisen EJ, Goodman MM, Namkoong G (eds) Proceedings of the Second International Conference on Quantitative Genetics. Sinauer, Sunderland, pp 505–522

    Google Scholar 

  • Mattson MP (2008) Awareness of hormesis will enhance future research in basic and applied neuroscience. Crit Rev Toxicol 38:633–639

    Article  CAS  PubMed  Google Scholar 

  • Mattson MP (2010) The fundamental role of hormesis in evolution. In: Mattson MP, Calabrese EJ (eds) Hormesis: A Revolution in Biology, Toxicology & Medicine. Humana Press, Inc., pp 213

  • Mattson MP, Maudsley S, Martin B (2004) BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders. Trends Neurosci 27:589–594

    Article  CAS  PubMed  Google Scholar 

  • Scheiner SM, Goodnight CJ (1984) The comparison of phenotypic plasticity and genetic variation in populations of the grass Danthonia spicata. Evolution 38:845–855

    Article  Google Scholar 

  • Scheiner SM, Lyman RF (1989) The genetics of phenotypic plasticity. I. heritability. J Evol Biol 2:95–107

    Article  Google Scholar 

  • Scheiner SM, Lyman RF (1991) The genetics of phenotypic plasticity. II. Response to selection. J Evol Biol 3:23–50

    Article  Google Scholar 

  • Scheiner SM, Caplan RL, Lyman RF (1991) The genetics of phenotypic plasticity. III. Genetic correlations and fluctuating asymmetries. J Evol Biol 4:51–68

    Article  Google Scholar 

  • Schlichting CD (1986) The evolution of phenotypic plasticity in plants. Ann Rev Ecol Syst 17:667–693

    Article  Google Scholar 

  • Schlichting CD, Levin DA (1984) Phenotypic plasticity in annual Phlox: Tests of some hypotheses. Amer J Bot 71:252–260

    Article  Google Scholar 

  • Schlichting CD, Levin DA (1986) Phenotypic plasticity: an evolving plant character. Biol J Linn Soc 29:37–47

    Article  Google Scholar 

  • Schlichting CD, Pigliucci M (1998) Phenotypic Evolution: A Reaction Norm Perspective. Sinauer Associates, Sunderland, MA, p 387

    Google Scholar 

  • Silva AJ, Zhou Y, Rogerson T, Shobe J, Balaji J (2009) Molecular and cellular approaches to memory allocation in neural circuits. Science 326:391–395

    Article  CAS  PubMed  Google Scholar 

  • Simons AM, Wagner I (2007) The characterization of complex continuous norms of reaction. Oikos 116:986–994

    Article  Google Scholar 

  • Van Tienderen PH (1991) Evolution of generalists and specialists in spatially heterogeneous environments. Evol 45:1317–1331

    Article  Google Scholar 

  • Via S (1987) Genetic constraints on the evolution of phenotypic plasticity. In: Loescheke V (ed) Genetic Constraints on Adaptive Evolution. Springer, Berlin, pp 47–71

    Google Scholar 

  • Via S, Lande R (1985) Genotype-environment interaction and the evolution of phenotypic plasticity. Evolution 39:505–523

    Article  Google Scholar 

  • Via S, Lande R (1987) Evolution of genetic variability in a spatially variable environment: effects of gentotype-environment interaction. Gen Res 49:147–156

    Article  CAS  Google Scholar 

  • Via S, Gomulkiewicz R, De Jong G, Scheiner SM, Schlichting CD, Van Tienderen PH (1995) Adaptive phenotypic plasticity: consensus and controversy. Trends Ecol Evol 10:212–217

    Article  CAS  PubMed  Google Scholar 

  • Zoladz PR, Diamond DM (2009) Linear and non-linear dose-response functions reveal a hormetic relationship between stress and learning. Dose-Response 7:132–148

    Google Scholar 

Figure 3 References

  • (1) Bodar CWM, Van Leeuwen CJ, Voogt PA, Zandee DI (1988) Effect of cadmium on the reproduction strategy of Daphnia magna. Aquat Toxicol 12:301–310

    Article  CAS  Google Scholar 

  • (2) Bors J, Zimmer K (1970) Effects of low doses of x-rays on rooting and yield of carnation. Stim Newsl 1:16–21

    Google Scholar 

  • (3) Brown RJ, Rundle SD, Hutchinson TH, Williams TD, Jones MB (2003) A copepod life-cycle test and growth model for interpreting the effects of lindane. Aquat Toxicol 63:1–11

    Article  CAS  PubMed  Google Scholar 

  • (4) Chapman RK, Allen TC (1948) Stimulation and suppression of some vegetable plants by DDT. J Econom Entomol 41(4):616–623

    CAS  Google Scholar 

  • (5) Cookson MR, Pentreath VW (1994) Alterations in the glial fibrillary acidic protein content of primary astrocyte cultures for evaluation of glial cell toxicity. Tox In Vitro 8:251–259

    Article  Google Scholar 

  • (6) Cookson MR, Mead C, Austwick SM, Pentreath VW (1995) Use of the MTT assay for estimating toxicity in primary astrocyte and C6 glioma cell cultures. Tox In Vitro 9:39–48

    Article  CAS  Google Scholar 

  • (7) De Nicola E, Gallo M, Iaccarino M, Meric S, Oral R, Russo T, Sorrentino T, Tunary O, Vuttariello E, Warnau M, Pagano G (2004) Hormetic versus toxic effects of vegetable tannin in a multitest study. Arch Environ Contam Toxicol 46:336–344

    Article  PubMed  Google Scholar 

  • (8) Gao X-M, Fukamauchi F, Chuang D-M (1993) Long-term biphasic effects of lithium treatment on phospholipase C-coupled M3-muscarinic acetylcholine receptors in cultured cerebellar granule cells. Neurochem Int 22(4):395–403

    Article  CAS  PubMed  Google Scholar 

  • (9) Gong P, Wilke B-M, Fleischmann S (1999) Soil-based phytotoxicity of 2, 4, 6-trinitrotoluene (TNT) to terrestrial higher plants. Arch Environ Contam Toxicol 36:152–157

    Article  CAS  PubMed  Google Scholar 

  • (10) Hodjat SH (1971) Effects of sublethal doses of insecticides and of diet and crowding of dysdercus fasciatus sign. (Hem., Pyrrhocoridae). Bull Entomol Res 60:367–378

    Article  CAS  Google Scholar 

  • (11) Ji L, Melkonian G, Riveles K, Talbot P (2002) Identification of pyridine compounds in cigarette smoke solution that inhibit growth of the chick chorioallantoic membrane. Toxicol Sci 69:217–225

    Article  CAS  PubMed  Google Scholar 

  • (12) Lin Q, Mendelssohn IA, Suidan MT, Lee K, Venosa AD (2002) The dose-response relationship between No. 2 fuel oil and the growth of the salt marsh grass, Spartina alterniflor. Mar Poll 44:897–902

    Article  CAS  Google Scholar 

  • (13) Liu P-S, Lin M-K (1997) Biphasic effects of chromium compounds on catecholamine secretion from bovine adrenal medullary cells. Toxicol 117:45–53

    Article  CAS  Google Scholar 

  • (14) Miller WM, Green CA, Kitchin H (1945) Biphasic action of penicillin and other sulphonamide similarity. Nature 1(155):210–211

    Article  Google Scholar 

  • (15) Nayak S, Mohanty RC, Mohanty L (1996) Growth rate off ankistrodesmus falcatus and Scenedesmus bijuga in mixed culture exposed to monocrotophos. Bull Environ Contam Toxicol 57:473–479

    Article  CAS  PubMed  Google Scholar 

  • (16) Nutman FJ, Roberts FM (1962) Stimulation of two pathogenic fungi by high dilutions of fungicides. Trans Br Mycol Soc 45(4):449–456

    Article  CAS  Google Scholar 

  • (17) Parkhurst BR, Bradshaw AS, Forte JL, Wright GP (1981) The chronic toxicity to Daphnia magna of acridine, a representative azarene present in synthetic fossil fuel products and wastewater. Environ Poll A 24:21–30

    Article  CAS  Google Scholar 

  • (18) Pollino CA, Holdway DA (1999) Potential of two hydra species as standard toxicity test animals. Ecotoxicol Environ Saf 43:309–316

    Article  CAS  PubMed  Google Scholar 

  • (19) Shamsi SRA, Sofajy SA (1980) Effects of low doses of gamma radiation on the growth and yield of two cultivar of broad bean. Environ Exper Bot 20:87–94

    Article  Google Scholar 

  • (20) Swaminathan MS, Murty BR (1959) Effect of x-radiation on pollen tube growth and seed setting in crosses between Nicotiana tabacum and N Rustica. Z Vererbungsl 90(3):393–399

    Article  CAS  PubMed  Google Scholar 

  • (21) Xiong Z-T, Peng Y-H (2001) Response of pollen germination and tube growth to cadmium with special reference to low concentration exposure. Ecotoxicol Environ Saf 48:51–55

    Article  CAS  PubMed  Google Scholar 

  • (22) Subhadra AV, Nanda AK, Behera PK, Panda BB (1991) Acceleration of catalase and peroxidase activities in Lemna minor L. and Allium cepa L. in response to low levels of aquatic mercury. Environ Poll 69:169–179

    Article  CAS  Google Scholar 

  • (23) Jefferson MC, Aguirre M (1980) Methanol tolerances and the effects of methanol on longevity and oviposition behavior in Drosophila pachea. Physiol Entomol 5:265–269

    Article  CAS  Google Scholar 

  • (24) Maisin JR, Wambersie A, Gerber GB, Mattelin G, Lambietcollier M, DeCoster B, Gueulette J (1988) Life-shortening and disease incidence in C57B1 mice after single and fractionated gamma and high-energy neutron exposure. Radiat Res 113:300–317

    Article  CAS  PubMed  Google Scholar 

  • (25) Wiedman SJ, Appleby AP (1972) Plant growth stimulation by sublethal concentrations of herbicides. Weed Res 12:65–74

    Article  CAS  Google Scholar 

  • (26) Ullrich RL, Storer JB (1979) Influence of γirradiation on the development of neoplastic disease in mice. Radiat Res 80:317–324

    Article  CAS  PubMed  Google Scholar 

  • (27) Abe T, Gotoh S, Higashi K (1999) Attenuation by glutathione of hsp72 gene expression induced by cadmium in cisplatin-resistant human ovarian cancer cells. Biochem Pharmacol 58:69–76

    Article  CAS  PubMed  Google Scholar 

  • (28) Rai UN, Gupta M, Tripathi RD, Chandra P (1998) Cadmium regulated nitrate reductase activity in Hydrilla verticillata (1.f.) Royle. Water Soil Air Poll 106:171–177

    Article  CAS  Google Scholar 

  • (29) Vieira VLP, Rocha JBT, Schetinger MRC, Morsch VM, Rodrigues SR, Tuerlinckz SM, Bohrer D, do Nascimento PC (2000) Effect of aluminum on δ-aminolevulinic acid dehydratase from mouse blood. Toxicol Lett 117:45–52

    Article  Google Scholar 

  • (30) Hamelink JL (1986) Toxicity of fluridone to aquatic invertebrates and fish. Environ Toxicol Chem 5:87–94

    Article  CAS  Google Scholar 

  • (31) Fong CJ, Sutkowski DM, Braun EJ, Bauer KD, Sherwood ER, Lee C, Kozlowski JM (1993) Effect of retinoic acid on the proliferation and secretory activity of androgen-responsive prostatic carcinoma cells. J Urol 149:1190–1194

    CAS  PubMed  Google Scholar 

  • (32) Hidalgo E, Dominquez C (2000) Growth-altering effects of sodium hypochlorite in cultured human dermal fibroblasts. Life Sci 67:1331–1344

    Article  CAS  PubMed  Google Scholar 

  • (33) Cicero TJ, Badger TM (1977) Effects of alcohol on the hypothalamic-pituitary-gonadal axis in the male rat. J Pharmacol Exp Ther 201:427–433

    CAS  PubMed  Google Scholar 

  • (34) Burris TP (1992) The stimulatory and inhibitory effects of dopamine on prolactin secretion involve different G-proteins. Endocrinology 130:926–932

    Article  CAS  PubMed  Google Scholar 

  • (35) Voss AK, Fortune JE (1993) Estradiol-17-β has a biphasic effect on oxytocin secretion by bovine granulose cells. Biol Reprod 48:1404–1409

    Article  CAS  PubMed  Google Scholar 

  • (36) Tang LL, Mamotte CDS, Van Bockxmeer FM, Taylor RR (1998) The effect of homocysteine on DNA synthesis in cultured human vascular smooth muscle. Atherosclerosis 136:169–173

    Article  CAS  PubMed  Google Scholar 

  • (37) Merkel LA, Lappe RW, Rivera LM, Cox BF, Perrone MH (1992) Demonstration of vasorelaxant activity with an A1-selective adenosine agonist in porcine coronary artery: Involvement of potassium channels. J Pharmacol Exp Ther 260:437–443

    CAS  PubMed  Google Scholar 

  • (38) McAnulty RJ, Hernandez-Rodriguez NA, Mutsaers SE, Coker RK, Laurent GJ (1997) Indomethacin suppresses the anti-proliferative effects of transforming growth factor-β isoforms on fibroblast cell cultures. Biochem J 321:639–643

    CAS  PubMed  Google Scholar 

  • (39) Meng G (1993) Effects of arsenic on DNA synthesis in human lymphocytes. Arch Environ Contam Toxicol 25:525–528

    Article  CAS  PubMed  Google Scholar 

  • (40) Poddar MK, Dewey WL (1980) Effects of cannabinoids on catecholamine uptake and release in hypothalamic and striatal synaptosomes. J Pharmacol Exp Ther 214:63–67

    CAS  PubMed  Google Scholar 

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Acknowledgement

Effort sponsored by the Air Force Office of Scientific Research, Air Force Material Command, USAF, under grant number FA9550-07-1-0248. This work was also supported by the Intramural Research Program of the National Institute on Aging, NIH. The U.S. Government is authorized to reproduce and distribute for governmental purposes notwithstanding any copyright notation thereon. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsement, either expressed or implied, of the Air Force Office of Scientific Research or the U.S. Government.

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

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