Abstract
There are a large number of exogenous biological and chemical substances with known neoplastic or carcinogenic potential. However, it has also been postulated that external stimuli can influence the body's internal milieu, and thereby induce compensatory excessive growth of cells in the form of hyperplasia or neoplasia. In a recent study, we observed a strong association between chronic hypoxic states and the occurrence of peripheral neuroblastic tumors, a relatively uncommon group of neural neoplasms. In this report we review those findings and formulate an hypothesis to explain why conditions which lead to chronic erythrocytosis may also cause compensatory neoplasia of neural tissues.
Similar content being viewed by others
References
Bernard, C.: Second Lecture, ‘The three forms of life’, In: Lectures on the Phenomena of Life Common to Animals and Plants, Charles C. Thomas, Springfield, 1974, pp. 46–91.
Seemayer, T. A., Thelmo, W. L., Bolande, R. P., and Wiglesworth, F. W.: ‘Peripheral neuroectodermal tumors’, Perspect. Pediatr. Pathol. 2 (1975), 151–172.
Kissel, P., André, J. M., and Jacquier, A.: ‘Von Recklinghausen's neurofibromatosis: Phakomatosis and neurocristopathy’, in The Neurocristopathies, Masson Publishing U.S.A., Inc., New York, 1981, pp. 223–232.
Christoferson, L. A., Gustafson, M. P., and Petersen, A. G.: ‘Von Hippel-Lindau's disease’, JAMA 178 (1961), 280–282.
Carney, J. A., Sizemore, G. W., and Sheps, S. G.: ‘Adrenal medullary disease in multiple endocrine neoplasia, type 2. Pheochromocytoma and its precursors’, Am. J. Clin. Pathol. 66 (1976), 279–290.
Thorling, E. B.: ‘Paraneoplastic erythrocytosis and inappropriate erythropoietin production. A review’, Scand. J. Haematol. Suppl 17, (1972) 1–166.
Shanklin, D. R. and Sotelo-Avila, C.: ‘In situ tumors in fetuses, newborns and young infants’, Biol. Neonat. 14, (1969) 286–316.
Guin, G. H., Gilbert, E. F., and Jones, B.: ‘Incidental neuroblastoma in infants’, Am. J. Clin. Pathol. 51, (1969) 126–136.
Miller, R. W., Fraumeni, J. F., Jr, and Hill, J. A.: ‘Neuroblastoma: Epidemiologic approach to its origin’, Am. J. Dis. Child. 115, (1968) 253–261.
Reisman, M., Goldenberg, E. D., and Gordon, J.: ‘Congenital heart disease and neuroblastoma’, Am. J. Dis. Child. 111, (1966) 308–310.
Reynolds, J. L. and Gilchrist, T. F.: ‘Congenital heart disease and pheochromocytoma’, Am. J. Dis. Child. 112, (1966) 251–255.
Folger, G. M., Jr, Roberts, W. C., Mehrizi, A., Shah, K. D., Glancy, D. L., Carpenter, C. C. J., and Esterly, J. R.: ‘Cyanotic malformations of the heart with pheochromocytoma. A report of five cases’, Circulation 29, (1964) 750–757.
Sy, W. M. and Edmonson, J. H.: ‘The developmental defects associated with neuroblastoma: Etiologic implications’, Cancer 22, (1968) 234–238.
de la Monte, S. M., Hutchins, G. M., and Moore, G. W.: ‘Peripheral neuroblastic tumors and congenital heart disease: Role of hypoxic states in tumor induction’, Am. J. Pediatr. Hematol. Oncol. (in press).
Gordon, A. S.: ‘Erythropoietin’, Vitam. Horm. 31, (1973) 105–174.
Gordon, A. S., Cooper, G. W., and Zanjani, E. D.: ‘The kidney and erythropoiesis’, Semin Hematol. 4, (1967) 337–358.
Fisher, J. W.: ‘Erythropoietin: Pharmacology, biogenesis and control of production’, Pharmacol. Rev. 24, (1971) 459–508.
Graber, S. E., and Krantz, S. B.: ‘Erythropoietin and the control of red cell production’, Annu. Rev. Med. 29, (1978) 51–66.
Metcalf, D.: ‘Hemopoietic colonies: In vitro cloning of normal and leukemic cells’, Recent Results Cancer Res. 61, (1977) 160–169.
Spivak, J. L., and Graber, S. E.: ‘Erythropoietin and the regulation of erythropoiesis’, Johns Hopkins Med. J. 146, (1980) 311–320.
Lange, R. D. and McDonald, T. P.: ‘Immunochemical studies of erythropoietin (ESF) and erythrogenin (REF)’, Acta Univ. Carol. Med. Suppl 2, (1971) 114–126.
Fagg, B.: ‘Is erythropoietin the only factor which regulates late erythroid differentiation?’, Nature 289, (1981) 184–186.
Fisher, J. W.: ‘Extrarenal erythropoietin production’, J. Lab. Clin. Med. 93, (1979) 695–699.
Beynon, G.: ‘The influence of the autonomic nervous system in the control of erythropoietin secretion in the hypoxic rat’, J. Physiol. 266, (1977) 347–360.
Faura, J., Ramos, J., Reynafarje, C., English, E., Finne, P., and Finch, C. A.: ‘Effect of altitude on erythropoiesis’, Blood 33, (1969) 668–676.
Cohen, R. A., Miller, M. E., Garcia, J. F., Moccia, G., and Cronkite, E. P.: ‘Regulatory mechanism of erythropoietin production: Effects of hypoxemia and hypercarbia’, Exp. Hematol. 9, (1981) 513–521.
Fisher, J. W., Samuels, A., and Langston J.: ‘Effects of angiotensin, norepinephrine and renal artery constriction on erythropoietin production’, Ann. NY. Acad. Sci. 149, (1968) 308–317.
Krantz, S. B. and Jacobson, L. O.: ‘Other humoral and nonhumoral influences on erythropoiesis’, in: Erythropoietin and the Regulation of Erythropoiesis, The University of Chicago Press, Chicago, Ill., 1970, pp. 149–166.
Peschle, C., Rappaport, I. A., Sasso, G. F., Gordon, A. S., and Condorelli, M.: ‘Mechanism of growth hormone (GH) action on erythropoiesis’, Endocrinology 91, (1972) 511–517.
Fisher, J. W.: ‘Prostaglandins and kidney erythropoietin production’, Nephron 25, (1980) 53–56.
Tramezzani, J. H., Morita, E., and Chiocchio, S. R.: ‘The carotid body as a neuroendocrine organ involved in control of erythropoiesis’, Proc. Natl. Acad. Sci. 68, (1971) 52–55.
Erslev, A. J., Caro, J., Miller, O., and Silver, R.: ‘Plasma erythropoietin in health and disease’, Ann. Clin. Lab. Sci. 10, (1980) 250–257.
Krantz, S. B., and Jacobson, L. O.: ‘Metabolism of erythropoietin’, in Erythropoietin and the Regulation of Erythropoiesis, The University of Chicago Press, Chicago, Ill., 1970, pp. 56–64.
Adamson, J. W., Alexanian, R., Martinez, C., and Finch, C. A.: ‘Erythropoietin excretion in normal man’, Blood 28, (1966) 354–364.
Krantz, S. B. and Jacobson, L. O.: ‘Pathological regulation of erythropoiesis’, in Erythropoietin and the Regulation of Erythropoiesis, The University of Chicago Press, Chicago, Ill., 1970, pp. 176–195.
Fried, W., Johnson, C., and Heller, P.: ‘Observations on regulation of erythropoiesis during prolonged periods of hypoxia’, Blood 36, (1970) 606–616.
Miller, M. E., Rorth, M., Parving H. H., Howard, D., Reddington, I., Valeri, C. R., and Stohlman, F., Jr: ‘pH effect on erythropoietin response to hypoxia’, N. Engl. J. Med. 288, (1973) 706–710.
Feldman, S., Rachmilewitz, E. A., and Izak, G.: ‘The effect of central nervous system stimulation on erythropoiesis in rats with chronically implanted electrodes’, J. Lab. Clin. Med. 67, (1966) 713–725.
Medado, P., Izak, G., and Feldman, S.: ‘The effect of electrical stimulation of the central nervous system on erythropoiesis in the rat. II. Localization of a specific brain structure capable of enhancing red cell production’, J. Lab. Clin. Med. 69, (1967) 776–786.
Crafts, R. C., and Meineke, H. A.: ‘The anemia of hypophysectomized animals’, Ann. NY. Acad. Sci. 77, (1959) 501–517.
Daughaday, W. D.: ‘The Adenohypophysis’, in Textbook of Endocrinology, Fifth edition, Williams, R. H., (ed.) Chapter 2, W. B. Saunders Co., Philadelphia, 1974, pp. 31–79.
Contopoulos, A. N., Ellis, S., Simpson, M. E., Lawrence, J. H., and Evans, H. M.: ‘Production of polycythemia in hypophysectomized rats by the pituitary erythropoietic factor’, Endocrinology 55, (1954) 808–812.
Fruhman, G. J., Gerstner, R., and Gordon, A. S.: ‘Effects of growth hormone upon erythropoiesis in the hypophysectomized rat’, Proc. Soc. Exp. Biol. Med. 85, (1954) 93–96.
Lehninger, A. L.: Biochemistry. The Molecular Basis of Cell Structure and Function, 2nd Edition, Worth Publishers, Inc. New York, 1978, pp. 189–195.
Adamson, J. W.: ‘The erythropoietin hematocrit relationship in normal and polycythemic man: Implications of marrow regulation’, Blood 32, (1968) 597–609.
Jindal, S. K., Gupta, G., Mohanty, D., Das, K. C., Bidwai, P. S., and Wahi, P. L.: ‘Study of erythropoiesis, erythropoietin and haematological adjustments in congenital cyanotic heart disease’, Indian J. Med. Res. 67, (1978) 1019–1028.
Waldmann, T. A., Levin, E. H., and Baldwin, M.: ‘The association of polycythemia with a cerebellar hemangioblastoma. The production of an erythropoiesis stimulating factor by the tumor’, Am. J. Med. 31 (1961) 318–324.
Morse, E. E.: ‘Consequences of erythropoietin production by neoplasms’, Ann. Clin. Lab. Sci. 9, (1979) 116–120.
Bradley, J. E., Young, J. D., Jr., and Lentz, G.: ‘Polycythemia secondary to pheochromocytoma’, J. Urol. 86, (1961) 1–6.
Gordon, A. S., Zanjani, E. D., and Zalusky, R.: ‘A possible mechanism for the erythrocytosis associated with hepatocellular carcinoma in man’, Blood 35, (1970) 151–157.
Carpenter, G., Schwartz, H., and Walker, A. E.: ‘Neurogenic polycythemia’, Ann. Intern. Med. 49, (1943) 470–481.
Rosse, W. F., Berry, R. J., and Waldmann, T. A.: ‘Some molecular characteristics of erythropoietin from different sources determined by inactivation by ionizing radiation’, J. Clin. Invest. 42, (1963) 124–129.
Nixon, R. K., O'Rourke, W., Rupe, C. E., and Korst, D. R.: ‘Nephrogenic polycythemia’, Arch. Intern. Med. 106, (1960) 797–802.
Rosse, W. F., and Waldmann, T. A.: ‘A comparison of some physical and chemical properties of erythropoiesis-stimulating factors from different sources’, Blood 24, (1964) 739–749.
Zanjani, E. D., Zalusky, R., and Wasserman, L. P.: ‘Erythropoietin (Ep)-releasing activity of serum from patients with polycythemia vera (PV) and tumor-associated erythrocytosis’, (Abstract), Clin. Res. 20, (1971) 878.
Raff, M. C., Abney, E., Brockes, J. P., and Hornby-Smith, A.: ‘Schwann cell growth factors’, Cell 15, (1978) 813–822.
Zamenhof, S., Mosley, J., and Schuller, E.: ‘Stimulation of the proliferation of cortical neurons by prenatal treatment with growth hormone’, Science 152 (1966) 1396–1397.
Sara, V. R., Lazarus, L., Stuart, M. C., and King, T.: ‘Fetal brain growth: Selective action by growth hormone’, Science 186, (1974) 446–447.
Author information
Authors and Affiliations
Additional information
Address correspondence and reprint requests to Professor Grover M. Hutchins, M.D., Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, 21205, U.S.A.
Supported by NIH Grants LM-03651 from the National Library of Medicine and HL-22963 from the National Heart, Lung and Blood Institute.
Rights and permissions
About this article
Cite this article
de la Monte, S.M., Hutchins, G.M. & Moore, G.W. Compensatory neoplasia: Chronic erythrocytosis and neuroblastic tumors. Theor Med Bioeth 5, 279–291 (1984). https://doi.org/10.1007/BF00489476
Issue Date:
DOI: https://doi.org/10.1007/BF00489476