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Hormesis: Once Marginalized, Evidence Now Supports Hormesis as the Most Fundamental Dose Response

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Hormesis

Abstract

The biomedical community made a fundamental error on the nature of the dose-response relationship early in the 20th century and has perpetuated this error to the present. The error was the byproduct of the conflict between homeopathy and traditional medicine. To deny support to homeopathy, leaders of the biomedical community rejected the hormetic biphasic dose-response model, the proposed explanatory principle of homeopathy. The threshold dose-response model was adopted as an alternative model, quickly becoming central to toxicology/pharmacology and their numerous applications. Despite its near-universal acceptance, no attempt was made to validate the ability of the threshold model to accurately predict responses in the below-threshold zone at the time of acceptance and throughout the 20th century. In contrast, the hormetic biphasic dose-response model became marginalized and was excluded from the mainstream of pharmacological/toxicological teaching and practice, textbook development, professional society journal publications, annual meeting presentations, grant funding, and use in government risk assessment. Over the last decade there has been a resurgence of interest in hormesis due to findings indicating that hormetic responses are common, reproducible, and generalizable, as well as independent of biological model, endpoint, and chemical class/physical stressor. Large-scale studies have indicated that the threshold model fails to accurately predict responses below the threshold, whereas the hormetic dose-response model performs very well. These findings indicate that the biomedical community made an error on the nature of the dose-response relationship, compromising the accuracy of toxicological and risk assessment practices, including environmental exposure standards, and impeding drug discovery/development and drug safety studies.

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References

  • Berliner H (1985) A System of Scientific Medicine. Philanthropic foundations in the Flexner era. New York: Tavistock Publications.

    Google Scholar 

  • Bliss CI (1935) The calculation of the dosage-mortality curve. Ann Appl Biol 22: 134–167.

    Article  CAS  Google Scholar 

  • Bohme H (1986) Hugo Schulz (8/6/1853–7/13/1932) his life and work. Dissertation from the Medical Department of the Free University of Berlin. Translated from the German by Julia M. Ryan, University of Massachusetts, Amherst.

    Google Scholar 

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

    Google Scholar 

  • Boyera N, Galey I, Bernard BA (1997) Biphasic effects of minoxidil on the proliferation and differentiation of normal human keratinocytes. Skin Pharmacol 10: 206–220.

    Article  CAS  PubMed  Google Scholar 

  • Branham SE (1929) The effects of certain chemical compounds upon the course of gas production by baker’s yeast. J Bacteriol 18: 247–264.

    CAS  PubMed  Google Scholar 

  • Bruce RD, Carlton WW, Ferber KH, Hughes DH, Quast JF, Salsburg DS, Smith JM (Members of the Society of Toxicology ED01 Task Force) (1981) Re-examination of the ED01 study—adjusting for time on study. Fund Appl Toxicol 1: 67–80.

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2008c) Alzheimer’s disease drugs: an application of the hormetic dose response model. Crit Rev Toxicol 38: 419–452.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2008 h) Drug therapies for stroke and traumatic brain injury often display U-shaped dose responses: occurrence, mechanisms and clinical implications. Crit Rev Toxicol 38: 557–577.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2008j) Hormesis and mixtures. Toxicol Appl Pharmacol 229: 262–263.

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2007) Threshold-dose-response model—RIP: 1911 to 2006. BioEssays 29: 686–688.

    Article  PubMed  Google Scholar 

  • Calabrese EJ (2005a) Historical blunders: how toxicology got the dose-response relationship half right. Cell Mol Biol 51: 643–654.

    CAS  PubMed  Google Scholar 

  • Calabrese EJ (2005b) Hormetic dose-response relationships in immunology: occurrence, quantitative features of the dose response, mechanistic foundations, and clinical implications. Crit Rev Toxicol 35: 89–295.

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2005c) 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 (2005d) Toxicological awakenings: the rebirth of hormesis as a central pillar of toxicology. Toxicol Appl Pharmacol 204: 1–8.

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2003a) Chemotherapeutics and hormesis. Crit Rev Toxicol 33: 305–354.

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2003b) Inorganics and hormesis. Crit Rev Toxicol 33: 215–304.

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2001a) Apoptosis: biphasic dose responses. Crit Rev Toxicol 31: 607–614.

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2001b) Cell migration/chemotaxis: biphasic dose responses. Crit Rev Toxicol 31: 524–615.

    Google Scholar 

  • Calabrese EJ (2001c) Dopamine: biphasic dose responses. Crit Rev Toxicol 31: 563–584.

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2001d) Nitric oxide: biphasic dose responses. Crit Rev Toxicol 31: 489–502.

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2001e) Estrogen and related compounds: biphasic dose responses. Crit Rev Toxicol 31: 503–516.

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2001f) Androgens: biphasic dose responses. Crit Rev Toxicol 31: 517–522.

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2001 g) 5-Hydroxytryptamine (serotonin): biphasic dose responses. Crit Rev Toxicol 31: 553–562.

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2001 h) Opiates: biphasic dose responses. Crit Rev Toxicol 31: 585–604.

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (2001i) Adrenergic receptors: biphasic dose responses. Crit Rev Toxicol 31: 523–538.

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ (1991) Multiple chemical interactions. Chelsea, MI: Lewis Publishers.

    Google Scholar 

  • Calabrese EJ (1985) Uncertainty factors and interindividual variation. Regul Toxicol Pharmacol 5: 190–196.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ, Baldwin LA (2003b) Chemotherapeutics and hormesis. Crit Rev Toxicol 33: 305–353.

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ, Baldwin LA (2002) Hormesis and high risk groups. Regul Toxicol Pharmacol 35: 414–428.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ, Baldwin LA (2000a) Chemical hormesis: its historical foundations as a biological hypothesis. Hum Exp Toxicol 19: 2–31.

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ, Baldwin LA (2000b) The marginalization of hormesis. Hum Exp Toxicol 19: 32–40

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ, Baldwin LA (2000c) Radiation hormesis: its historical foundations as a biological hypothesis Hum Exp Toxicol 19: 41–75.

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ, Baldwin LA (2000d) Radiation hormesis: the demise of a legitimate hypothesis. Hum Exp Toxicol 19: 76–84.

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ, Baldwin LA (2000e) Tales of two similar hypotheses: the rise and fall of chemical and radiation hormesis. Hum Exp Toxicol 19: 85–97.

    Article  CAS  PubMed  Google Scholar 

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

    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, Bachmann KA, Bailer AJ, Bolger PM, Borak J, Cai L, Cedergreen N, Cherian MG, Chiueh CC, Clarkson TW, Cook RR, Diamon DM, Doolittle DJ, Dorato MA, Duke SO, Feinendegen L, Gardner DE, Hart RW, Hastings KL, Hayes AW, Hoffmann GR, Ives JA, Jaworowski Z, Johnson TE, Jonas WB, Kaminski NE, Keller JG, Klaunig JE, Knudsen TB, Kozumbo WJ, Lettieri T, Liu S-Z, Maisseu A, Maynard KI, Masoro EJ, McClellan RO, Mehendale HM, Mothersill C, Newlin DB, Nigg HN, Oehme FW, Phalen RF, Philbert MA, Rattan SIS, Riviere JE, Rodricks J, Sapolsky RM, Scott BR, Seymour C, Sinclair DA, Smith-Sonneborn J, Snow ET, Spear L, Stevenson DE, Thomas Y, Tubiana M, Williams GM, Mattson MP (2007) Biological stress response terminology: integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework. Toxicol Appl Pharmacol 222: 122–128.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Calder WA (1996) Size, function, and life history Mineola, NY: Dover Publications.

    Google Scholar 

  • Chueh S-C, Guh J-H, Chen J, Lai M-K, Teng C-M (2001) Dual effects of ouabain on the regulation of proliferation and apoptosis in human prostatic smooth muscle cells. J Urol 166: 347–353.

    Article  CAS  PubMed  Google Scholar 

  • 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 

  • Clark AJ (1937) Handbook of experimental pharmacology. Berlin: Verlag Julius Springer.

    Google Scholar 

  • Clark AJ (1933) Mode of action of drugs on Cells. London: Arnold.

    Google Scholar 

  • Clark AJ (1927) The historical aspects of quackery, Part 2. Br Med J 2: 960.

    Article  Google Scholar 

  • 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. Toxicol in Vitro 9: 39–48.

    CAS  Google Scholar 

  • Crump T (2003) Contemporary medicine as presented by its practitioners themselves, Leipzig, 1923:217–250. Hugo Schulz. Nonlinearity Biol Toxicol Med 1: 295–318

    Article  PubMed  Google Scholar 

  • Davies, JMS, Lowry, CV, and Davies, KJA (1995) Transient adaptation to oxidative stressing yeast. Arch Biochem Biophys 317: 1–6.

    Article  CAS  PubMed  Google Scholar 

  • Flexner A (1910) Medical education in the United States and Canada. A report to the Carnegie Foundation for the Advancement of Teaching. New York.

    Google Scholar 

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

    Article  CAS  PubMed  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 

  • Foekens JA, Sieuwerts AM, Stuurman-Smeets EMJ, Dorssers LCJ, Berns EMJJ, Klijn JGM (1992) Pleiotropic actions of suramin on the proliferation of human breast cancer cells in vitro. Int J Cancer 51: 439–444.

    Article  CAS  PubMed  Google Scholar 

  • Foley GE,, Winter WD (1949) Increased mortality following penicillin therapy of chick embryos infected with Candida albicans var Stellatoidea. J Infect Dis 85: 268–274.

    CAS  PubMed  Google Scholar 

  • Fornaro E, Li D, Pan J, Belik J (2007) Prenatal exposure to fluoxetine induces fetal pulmonary hypertension in the rat. Am J Respir Crit Care Med 176: 1035–1040.

    Article  CAS  PubMed  Google Scholar 

  • Fukushima S, Kinoshita A, Puatanachokchai R, Kushida M, Wanibuchi H, Morimura K (2005) Hormesis and dose-response-mediated mechanisms in carcinogenesis: evidence for a threshold in carcinogenicity of non-genotoxic carcinogens. Carcinogenesis 26: 1835–1845.

    Article  CAS  PubMed  Google Scholar 

  • Gaddum JH (1962) Pharmacologists of Edinburgh. Annu Rev Pharmacol Toxicol 2: 1–10.

    CAS  Google Scholar 

  • Gaddum JH (1933) Methods of biological assay depending on the quantal response. London: His Majesty’s Stationery Office.

    Google Scholar 

  • Garrod LP (1951) The reactions of bacteria to chemotherapeutic agents. Br Med J 1: 205–210.

    Article  CAS  PubMed  Google Scholar 

  • Giuliani N, Pedrazzoni M, Negri G, Passeri G, Impicciatore M, Girasole G (1998) Bisphosphonates stimulate formation of osteoblast precursors and mineralized nodules in murine and human bone marrow cultures in vitro and promote early osteoglastogenesis in young and aged mice in vivo. Bone 22: 455–461.

    Article  CAS  PubMed  Google Scholar 

  • Goerig M, Agarwal K, Esch JS (2000) The versatile August Bier (1861–1949), father of spinal anesthesia. J Clin Anesth 12: 561–569.

    Article  CAS  PubMed  Google Scholar 

  • Honar H, Riazi K, Homayoun H, Sadeghipour H, Rashidi N, Ebrahimkhani MR, Mirazi N, Dehpour AR (2004) Ultra-low dose naltrexone potentiates the anticonvulsant effect of low dose morphine on clonic seizures. Neuroscience 129: 733–742.

    Article  CAS  PubMed  Google Scholar 

  • Hunter PE, Krithayakiern V (1971) Effect of gamma radiation upon life expectancy and reproduction in the house cricket, Acheta domesticus (orthopter: Gryllidae). Ann Entomol Soc Am 64: 119–123.

    Google Scholar 

  • Im HK, Im WB, Pregenzer JF, Carter DB, Jacobsen EJ, Hamilton BJ (1995) Characterization of U-97775 as a GABAA receptor ligand of dual functionality in cloned rat GABAA receptor subtypes. Br J Pharmacol 115: 19–24.

    CAS  PubMed  Google Scholar 

  • Jacobsen EJ, TenBrink RE, Stelzer LS, Belonga KL, Carter DB, Im HK, Im WB, Sethy VH, Tang AH, VonVoigtlander PF, Petke, JD (1996a) High affinity partial agonist imidazol[1,5-a]quinoxaline amides, carbamate, and ureas at the γ-aminobutyric acid A/benzodiazepine receptor complex. J Med Chem 39: 158–175.

    Article  CAS  PubMed  Google Scholar 

  • Jacobsen EJ, Stelzer LS, Belonga KL, Carter DB, Im WB, Sethy VH, Tang AH, VonVoigtlander PF, Petke JD (1996b) 3-Phenyl-substituted imidazo[1,5-a]quinoxalin-4-ones and imidazol[1,5-a]quinoxaline ureas that have high affinity at the GABAA/benzodiazepine receptor complex. J Med Chem 39: 3820–3836.

    Article  CAS  PubMed  Google Scholar 

  • Jacobsen EJ, Stelzer LS, TenBrink RE, Belonga KL, Carter DB, Im HK, Im WB, Sethy VH, Tang AH, VonVoigtlander PF, Petke JD, Zhong WZ, Mickelson JW (1999) Piperazine imidazo[1,5-a]quinoxaline ureas as high-affinity GABAA ligands of dual functionality. J Med Chem 42: 1123–1144.

    Article  CAS  PubMed  Google Scholar 

  • Lee JB, Hayashi K, Hayashi T, Sankawa U, Maeda M (1999) Antiviral activities against HSV-1, HCMV, and HIV-1 of rhamnan sulfate from Monostroma latissimum. Planta Med 65: 439–441.

    Article  PubMed  Google Scholar 

  • Lehman AJ (1954) Untitled. Assoc Food Drug Off 18: 33.

    Google Scholar 

  • Liberman UA, Weiss SR, Broll J, Minne HW, Quan H, Bell NH, Rodriguezportales J, Downs RW, Dequeker J, Favus M, Seeman E, Recker RR, Capizzi T, Santora AC, Lombardi A, Shah RV, Hirsch LJ, Karpf DB (1995) Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Engl J Med 333: 1437–1443.

    Article  CAS  PubMed  Google Scholar 

  • McGaugh JL, Petrinovich LF (1965) Effects of drugs on learning and memory. Int Rev Neurobiol 8: 139–196.

    Article  CAS  PubMed  Google Scholar 

  • Melchior CL, Ritzmann RF (1994) Dehydroepiandrosterone is an anxiolytic in mice on the plus maze. Pharmacol Biochem Behav 47: 427–441.

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • 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 

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

    Article  CAS  Google Scholar 

  • Murrell GAC, Francis MJO, Bromley L (1990) Modulation of fibroblast proliferation by oxygen free radicals. Biochem J 265: 659–665.

    CAS  PubMed  Google Scholar 

  • Murry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 75: 534–537.

    Google Scholar 

  • Mutscheller A (1925) Physical standards of protection against Roentgen ray dangers. Am J Roentgenol 13: 65–69.

    Google Scholar 

  • National Academy of Sciences (NAS) (1977) Drinking water and health. Washington, DC: National Academy of Sciences.

    Google Scholar 

  • National Council on Radiation Protection and Measurements (NCRPM) (1954) Permissible dose from external sources of ionizing radiation. Washington, DC: U.S. Department of Commerce.

    Google Scholar 

  • Nyberg K, Ekblad M, Bergstrom T, Freeman C, Parish CR, Ferro V, Trybala E (2004) The low molecular weight heparin sulfate-mimetic, PI-88, inhibits cell-to-cell spread of herpes simplex virus. Antiviral Res 63: 15–24.

    Article  CAS  PubMed  Google Scholar 

  • Paalzow GHM, Paalzow LK (1985) Promethazine both facilitates and inhibits nociception in rats: effect of the testing procedure. Psychopharmacology 85: 31–36.

    Article  CAS  PubMed  Google Scholar 

  • Paalzow GHM, Paalzow LK (1983a) Opposing effects of apomorphine on pain in rats. Evaluation of the dose-response curve. Eur J Pharmacol 88: 27–35.

    Article  CAS  PubMed  Google Scholar 

  • Paalzow GHM, Paalzow LK (1983b) Yohimbine both increases and decreases nociceptive thresholds in rats evaluation of the dose-response relationship. Naunyn-Schmied Arch Pharmacol 322: 193–197.

    Article  CAS  Google Scholar 

  • 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 Pollut (Series A) 24: 21–30.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Randall WA, Price CW, Welch H (1947) Demonstration of hormesis (increase in fatality rate) by penicillin. Am J Public Health 37: 421–425.

    Article  PubMed  Google Scholar 

  • Rossini M, Gatti D, Zamberlan N, Braga V, Dorizzi R, Adami S (1994) Long-term effects of a treatment course with oral alendronate of postmenopausal osteoporosis. J Bone Miner Res 9: 1833–1837.

    Article  CAS  PubMed  Google Scholar 

  • Sandifer RD, Hopkin SP (1997) Effects of temperature on the relative toxicities of Cd, Cu, Pb, and Zn to Folsomia candida (collembolan). Ecotoxicol Environ Safety 37: 125–130

    Article  CAS  PubMed  Google Scholar 

  • Schulz H (1888) Uber Hefegifte. Pfluger’s Archiv Gesamte Physiol 42: 517–541.

    Article  Google Scholar 

  • Schulz H (1885) About the treatment of cholera nostras with veratrine [in German].Deutsch Arzneipflanzen Forsch Wochenzeit 11: 99–100. [Translated by Julia M. Ryan, University of Massachusetts, Amherst.]

    Google Scholar 

  • Southam CM, Ehrlich J (1943) Effects of extract of Western red-cedar heartwood on certain wood-decaying fungi in culture. Phytopathology 33: 517–524.

    Google Scholar 

  • Starke K (1998) A history of Naunyn-Schmiedeberg’s Archives of Pharmacology. Naunyn-Schmied Arch Pharmacol 358: 1–109.

    Article  CAS  Google Scholar 

  • Sukata T, Uwagawa S, Ozaki K, Ogawa M, Nishikawa T, Iwai S, Kinoshita A, Wanibuchi H, Imaoka S, Funae Y, Okuno Y, Fukushima S (2002) Detailed low-dose study of 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane carcinogenesis suggests the possibility of a hormetic effect. Int J Cancer 99: 112–118.

    CAS  Google Scholar 

  • Ungar J, Muggleton P (1946) The effect of penicillin on the growth of human type M tuberculosis. J Pathol Bacteriol 58: 501–504.

    Article  CAS  PubMed  Google Scholar 

  • U.S. Environmental Protection Agency (U.S. EPA) (1986) Guidelines for the health risk assessment of chemical mixtures. Fed Regist 57: 34014–34025.

    Google Scholar 

  • Verney EB, Barcroft J (1941) AJ Clark (Obituary). Obituary Notices Fellows. Roy Soc 3: 969.

    Google Scholar 

  • 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 

  • Welch H, Price CW, Randall WA (1946) Increase in fatality rate of E. typhosa for white mice by streptomycin. J Am Pharmaceut Assoc 35: 155–158.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Wise LE, Lichtman AH (2007) The uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist memantine prolongs spatial memory in a rat delayed radial-arm maze memory task. Eur J Pharmacol 575: 98–102.

    Article  CAS  PubMed  Google Scholar 

  • Wu W-C, Kao Y-H, Hu D-N (2002) A comparative study of effects of antiproliferative drugs on human retinal pigment epithelial cells in vitro. J Ocular Pharmacol Ther 18: 251–264.

    Article  CAS  Google Scholar 

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Acknowledgment s

This work was sponsored by the Air Force Office of Scientific Research, Air Force Material Command, USAF, under grant number FA9550-07-1-0248. The U.S. Government is authorized to reproduce and distribute reprints for governmental purposes notwithstanding any copyright notation hereon. The views and conclusions contained herein are those of the author 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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  1. Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, 01003, Amherst, MA, USA

    Edward J. Calabrese

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  1. Lab. Neurosciences, National Institute on Aging, Nathan Shock Drive 5600, Baltimore, 21224, U.S.A.

    Mark P. Mattson

  2. Dept. Environmental Health Sciences, University of Massachusetts, Morrill Science Center N344, Amherst, 01003-5712, U.S.A.

    Edward J. Calabrese

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Calabrese, E.J. (2010). Hormesis: Once Marginalized, Evidence Now Supports Hormesis as the Most Fundamental Dose Response. In: Mattson, M., Calabrese, E. (eds) Hormesis. Humana Press. https://doi.org/10.1007/978-1-60761-495-1_2

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