Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Chemically induced esthesioneuroepithelioma: a cytogenetic, cell culture and biochemical investigation with implications for tumor histogenesis

  • 14 Accesses

  • 3 Citations


Chemically induced esthesioneuroepitheliomas (ENE) in rats were subjected to tissue culture experiments, biochemical evaluations for catecholamines and chromosomal analyses. The most conspicuous cytogenetic finding was a C1 marker chromosome in addition to numerical and structural chromosomal aberrations. Regarding the overwhelming similarity between human ENE and experimentally induced ENE, similar cytogenetic aberrations in its human counterpart are postulated. Biochemically, no catecholamines or their metabolic precursors could be identified, thus distinguishing ENE from sympathetic neuroblastomas. No keratin-positive cells could be found in the primary tumor or in the cell cultures studied, thus showing that immunohistology can be a valuable tool for differentiating ENE from anaplastic carcinomas.

This is a preview of subscription content, log in to check access.


  1. 1.

    Atkin NB, Baker MS (1982) Non random chromosome changes in carcinoma of the cervix uteri. I. Nine near diploid tumors. Cancer Genet Cytogenet 7:209–222

  2. 2.

    Atkin NB, Pickthall VJ (1977) Chromosome 1 in 14 ovarian cancers. Heterochromatin variants and structural changes. Hum Genet 38:25–33

  3. 3.

    Barnes JM, Magee PN (1954) Some toxic properties of dimethylnitrosamine. Br J Ind Med 11:167–174

  4. 4.

    Brodeur GM, Sekhon GL, Goldstein MN (1977) Chromosomal aberrations in human neuroblastomas. Cancer 40:2256–2263

  5. 5.

    Brodeur GM, Green AA, Hayes FA (1980) Cytogenetic studies of primary human neuroblastomas. In: Evans AE (ed) Advances in neuroblastoma research. Raven Press, New York, pp 77–80

  6. 6.

    Cantrell R, Ghorayet BY, Fitz-Hugh GS (1977) Esthesioneuroblastoma. Diagnosis and treatment. Ann Otol 86:760

  7. 7.

    Chaudhry AP, Haar JG, Koul A, Nickerson P (1979) Olfactory neuroblastoma (esthesioneuroblastoma). A light and ultrastructural study of two cases. Cancer 44:564

  8. 8.

    Druckrey H, Schmähl D (1962) Erzeugung von Lungenkrebs durch subkutane Injektion von N-Diamylnitrosamin an Ratten. Naturwissenschaften 49:119

  9. 9.

    Druckrey H, Preussmann R, Schmäl D, Müller M (1961) Chemische Konstitution und karzinogene Wirkung bei Nitrosaminen. Naturwissenschaften 48:134

  10. 10.

    Druckrey H, Preussmann R, Blum G, Ivankovic S (1963) Karzinogene Wirkung von Diazoessigestern und von N-Nitrososarkosinestern als Beispiel für das Prinzip: Transport und Wirkform. Naturwissenschaften 50:99

  11. 11.

    Druckrey H, Ivankovic S, Memel HD, Preussmann R (1964) Selektive Erzeugung von Karzinomen der Nasenhöhle bei Ratten durch N-N′-Di-Nitrosopiperazin, Nitrosopiperidin, Nitrosomorpholin, Methyl-Allyl-, Dimethyl- und Methylamyl-Nitrosamin. Z Krebsforsch 66:138–150

  12. 12.

    Druckrey H, Preussmann R, Ivancovic S, Schmähl D (1967) Organotrope karzinogene Wirkung bei 65 verschiedenen N-Nitrosoverbindungen an BD-Ratten. Z Krebsforsch 69:103–201

  13. 13.

    Greenberg R, Rosenthal J, Falk GS (1969) Electron microscopy of human tumors secreting catecholamines: correlation with biochemical data. J Neuropathol Exp Neurol 28:475–500

  14. 14.

    Herrold McDK (1964) Induction of olfactory neuroepithelial tumors in Syrian hamsters by diethylnitrosamine. Cancer 17:114

  15. 15.

    Herrold McDK, Dunham LJ (1963) Induction of tumors in the Syrian hamster with diethylnitrosamine (N-nitrosodiethylamine). Cancer Res 23:773

  16. 16.

    Hunneman DH (1983) Mass fragmentographic determination of homovanillic and 4-hydroxy-3-methoxy mandelic acid in 50 μl plasma. Clin Chem Acta 135:169–174

  17. 17.

    Jung H, Gutjahr P (1977) Kindliche Malignoma im HNO-Bereich. In: Berendes J, Link P, Zöllner F (eds) HalsNasen-Ohren-Heilkunde in Praxis und Klinik, vol 2. Obere und untere Luftwege. Thieme, Stuttgart New York

  18. 18.

    Kameya T, Shimosato Y (1980) Neuroendocrine carcinoma of the paranasal sinus. A morphological and endocrinological study. Cancer 45:330–339

  19. 19.

    Käser H (1972) Biochemische Diagnostik des Phäochromocytoms, des Neuroblastoms und anderer neuroektodermaler Neoplasien. Helv Paediatr Acta [Suppl] 29:1–114

  20. 20.

    Kovacs G (1978) Abnormalities of chromosome 1 in human solid malignant tumors. Int J Cancer 21:688–694

  21. 21.

    Lijinsky W, Taylor HW (1975) Tumorigenesis by oxygenated nitrosopiperidines in rats. J Natl Cancer Inst 55:705–708

  22. 22.

    Lijinsky W, Taylor HW (1975) Carcinogenicity of methylated nitrosopiperidines. Int J Cancer 16:318–322

  23. 23.

    Lijinsky W, Taylor HW (1975) Increased carcinogenicity of 2,6-dimethylnitrosomorpholine compared with nitrosomorpholines in rats. Cancer Res 35:2123–2125

  24. 24.

    Makino S (1952) Cytological studies on cancer. III. The characteristics and individuality of chromosomes in tumor cells of the Yoshida sarcoma which contribute to the growth of the tumor. Gann 43:17–34

  25. 25.

    Makino S (1952) A cytological study of the Yoshida sarcoma, an ascites tumor of rats. Chromosoma 4:649–674

  26. 26.

    Makino S (1957) The concept of stem line cells as progenitors of a neoplastic population. Cytologia (Tokyo) [Suppl] 1:177–181

  27. 27.

    Micheau C (1977) A new histochemical and biochemical approach to olfactory esthesioneuroma. A nasal tumor of neural crest origin. Cancer 40:314–318

  28. 28.

    Micheau C, Guerinot F, Bohnon C, Brugge J (1975) Dopamine-B-hydroxylase and catecholamines in an olfactory esthesioneuroma. Cancer 35:1309–1312

  29. 29.

    Misugi K, Misugi N, Newton WA (1968) Fine structural study of neuroblastoma, ganglioneuroblastoma and pheochromocytoma. Arch Pathol 86:160–170

  30. 30.

    Mitelman F (1983) Catalogue of chromosome aberrations in cancer. In: Klinger HP (ed) Cytogenetics and cell genetics. Karger, Basel, pp 21–27

  31. 31.

    Mohr U, Althoff J, Page N (1972) Tumors in the respiratory system induced in the common European hamster by N-diethylnitrosamine. J Natl Cancer Inst 49:595–597

  32. 32.

    Mohr U, Reznik G, Pour P (1977) Carcinogenic effects of Diisopropanolnitrosamine in Sprague-Dawley rats. J Natl Cancer Inst 58:361–366

  33. 33.

    Pfeiffer RA (1974) Cell cultures from blood and bone marrow. In: Schwarzacher HG, Wolf U (eds) Methods in human cytogenetics. Springer, Berlin Heidelberg New York

  34. 34.

    Popoff N, Elsworth RM (1969) The fine structure of nuclear alterations in retinoblastoma and in the developing human retina: in vivo and in vitro observations. J Ultrastruct Res 29:535

  35. 35.

    Popoff N, Elsworth RM (1971) The fine structure of retinoblastoma. In vivo and in vitro observations. Lab Invest 25:389

  36. 36.

    Povlsen CO, Visfeldt J, Rygaard J, Jense G (1975) Growth pattern and chromosome constitution of human malignant tumors after long term serial transplantation in nude mice. Acta Pathol Microbiol Scand [A] 83:709–716

  37. 37.

    Preussmann R (1975) Chemische Carcinogenese in der menschlichen Umwelt. In: Grundmann (ed) Handbuch der allgemeinen Pathologie, vol VI/6, part 2. Springer, Berlin Heidelberg New York, pp 421–594

  38. 38.

    Reznik-Schüller H (1977) Ultrastructural alterations of APUD cells during nitrosamine-induced lung carcinogenesis. J Pathol 121:79

  39. 39.

    Reznik-Schüller H (1978) Ultrastructure of N-diethylnitrosamine induced tumors in the olfactory region of the Syrian golden hamster. J Pathol 124:161

  40. 40.

    Reznik-Schüller H, Mohr U (1976) Ultrastructure of N-nitrosodibutylamine induced tumors of the nasal cavities in the European hamster. J Natl Cancer Inst 57:401–407

  41. 41.

    Reznik G, Ulland B, Stinson SF, Ward JM (1980) Morphology and sex-dependent manifestation of nasal tumors in B6C3F1 mice after chronic inhalation of 1,2 dibromo-3-chloropropene. J Cancer Res Clin Oncol 98:75–83

  42. 42.

    Sandberg AA (1980) The chromosomes in human cancer and leukemia. Elsevier, New York

  43. 43.

    Schwarzacher HG (1974) Preparation of metaphase chromosomes. In: Schwarzacher HG, Wolf U (eds) Methods in human cytogenetics. Springer, Berlin Heidelberg New York

  44. 44.

    Shimosato Y, Kameya T, Hayashi H, Kubota T, Jida S, Hirohashi S, Mukojima T (1978) Experimental chemotherapy on human tumors transplanted in nude mice with particular reference to evaluation of results by tumor products. In: Houchens DP, Ovejera AA (eds) The use of athymic (nude) mice in cancer research. Fischer, Stuttgart, pp 195–206

  45. 45.

    Spörri PE, Dresp W, Heyder E (1982) Modified growth cones in mouse neuroblastoma cultures. An electron microscopic study. J Hirnforsch 23:287–293

  46. 46.

    Starck D (1975) Embryologie. Ein Lehrbuch auf allgemein biologischer Grundlage. Thieme, Stuttgart

  47. 47.

    Sugihara S (1981) Morphological studies on tumors of the nasal cavity induced in rats by N-Nitrosopiperidine. No To Shinkei 33:679–692

  48. 48.

    Tannenbaum M (1970) Ultrastructural pathology of adrenal medullary tumors. Pathol Ann 5:145–171

  49. 49.

    Thomas C (1965a) Durch Nitrosamine experimentell erzeugte Nasenhöhlentumoren bei der Ratte. Verh Dtsch Ges Pathol 49:245–248

  50. 50.

    Thomas C (1965b) Zur Morphologie der Nasenhöhlentumoren bei der Ratte. Z Krebsforsch 67:1–10

  51. 51.

    Ts'O MOM, Fine BS, Zimmermann LE (1969) The Flexner Winterstein rosettes in retinoblastoma. Arch Pathol 88:664

  52. 52.

    Ts'O MOM, Fine DS, Zimmermann LE (1970) The nature of retinoblastoma. II. Photoreceptor differentiation: an electronmicroscopic study. Am J Ophthalmol 69:350

  53. 53.

    Ueyama Y, Morita K, Yokoyama M, Kondo Y, Tamaoki N, Izumi S, Hata J, Ohsawa J (1976) Establishment and maintenance of human malignant tumors serially transplanted to nude mice. In: Nomura T, Ohsawa N, Tamaoki N, Fujiwara K (eds) Proceedings of the Second International Workshop on Nude Mice. Fischer, New York, pp 405–416

  54. 54.

    Vollrath M (1984) Histogenese des Ästhesio (olfactorius) neuroepithelioms — eine tierexperimentelle Studie an chemisch induzierten Tumoren der Ratte. Habilitationsschrift, Göttingen

  55. 55.

    Vollrath M, Altmannsberger M (1989) Chemically induced esthesioneuroepithelioma: ultrastructural findings. Ann Otol Rhinol Laryngol (in press)

  56. 56.

    Vollrath M, Altmannsberger M (1989) Ästhesioneuroepitheliom: Histogenese und Diagnose. Strahlenther Onkol (in press)

  57. 57.

    Vollrath M, Altmannsberger M, Hunnemann DH, Goebel HH, Osborn M (1984) Esthesioneuroblastoma: ultrastructural, immunohistological and biochemical investigation of one case. Arch Otorhinolaryngol 239:133

  58. 58.

    Vollrath M, Altmannsberger M, Weber K, Osborn M (1985) An ultrastructural and immunohistological study of the rat olfactory epithelium: unique properties of olfactory sensory cells. Differentiation 29:243

  59. 59.

    Vollrath M, Altmannsberger M, Weber K, Osborn M (1986) Chemically induced tumors of rat olfactory epithelium — a model for human esthesioneuroepithelioma. J Natl Cancer Inst 76:1205

  60. 60.

    Weichselbaum RR, Zakov ZN, Alter DM, Friedman AH (1979) New findings in the chromosome 13 long arm deletion syndrome and retinoblastoma. Ophthalmology 86:1191–1198

  61. 61.

    Weisburger DH, Williams GM (1980) Chemical carcinogenesis. In: Doull J, Klaassen CD, Amdur MO (eds) Toxicology: the basic science of poisons. Academic Press, New York

  62. 62.

    Whang-Peng J, Bum PA, Koa-Shan CS, Lee EC, Carney DN, Gazdar A, Minna JD (1982) A nonrandom chromosomal abnormality, del 3p (14–23) in human small cell lung cancer. Cancer Genet Cytogenet 6:119–134

  63. 63.

    Yamada K, Kondo T, Yoshida M, Oami H (1980) Cytogenetic studies in twenty human brain tumors: association of No. 22 chromosome abnormalities with tumors of the brain. Cancer Genet Cytogenet 2:293–307

  64. 64.

    Yosida TH (1975) Chromosomal alterations and development of experimental tumors. In: Grundmann E (ed) Handbuch der allgemeinen Pathologie. Springer, Berlin Heidelberg New York, pp 667–753

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Vollrath, M. Chemically induced esthesioneuroepithelioma: a cytogenetic, cell culture and biochemical investigation with implications for tumor histogenesis. Arch Otorhinolaryngol 246, 71–78 (1989).

Download citation

Key words

  • Esthesioneuroepithelioma
  • Marker chromosome
  • Cell culture
  • Catecholamines
  • Immunohistology