Summary
In an attempt to eludicate the histogenesis of thyroid carcinoma, histopathological and immunohistological studies were conducted on rat thyroid tumors induced by diisopropanolnitrosamine (DIPN). A total of 235 nodular lesions detected on serial sections of whole thyroid glands were classified into three types as follows: foci of cellular alteration at the single follicle level (type 1); multifollicular nodules considered to be malignant or potentially malignant (type 3); and multifollicular, proliferative nodules other than type 3, including both hyperplastic and neoplastic nodules (type2). Analysis of the frequency of nodular lesions after various periods of time following exposure to DIPN revealed that the size of the nodules, their pattern of development, and their growth activity, as measured by the labeling index for bromodeoxyuridine (BrdU), showed sequential changes. Type 1 lesions appeared early; these lesions were the smallest and were considered to indicate the initial morphological change. Subsequently, type 2 nodules of intermediate size and labeling index, and finally type 3 nodules with the largest size and the highest labeling index developed; the latter type 3 nodules become more numerous during the latest phase following DIPN exposure. These observations support a multistage hypothesis of tumorigenesis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aldaz CM, Conti CJ, Klein-Szanto AJP, Slaga TJ (1987) Progressive dysplasia and aneuploidy are hallmarks of mouse skin papillomas: relevance to malignancy. Proc Natl Acad Sci USA 84:2029–2032
Chou MY, Chang ALC, McBride J, Donoff B, Gallagher GT, Wong DTW (1990) A rapid method to determine proliferation patterns of normal and malignant tissues by H3 mRNA in situ hybridization. Am J Pathol 136:729–733
Gratzner HG (1982) Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: a new reagent for detection of DNA replication. Science 218:474–475
Hiasa Y, Kitahori Y, Enoki N, Konishi N, Shimoyama T (1984) 4,4'-Diaminodiphenylmethane: promoting effect on the development of thyroid tumors in rats treated with N-bis(2-hydroxypropyl) nitrosamine. JNCI 72:471–476
Hiasa Y, Kitahori Y, Konishi N, Shimoyama T, Lin J-C (1985) Sex differential and dose dependence of phenobarbital-promoting activity in N-bis(2-hydroxypropyl) nitrosamine-initiated thyroid tumorigenesis in rats. Cancer Res 45:4087–4090
Kawaoi A, Moriyama S (1987a) Diisopropanolnitrosamine (DIPN) induced rat thyroid lesions I. A histological classification. Acta Pathol Jpn 37:965–973
Kawaoi A, Moriyama S (1987b) Diisopropanolnitrosamine (DIPN) induced rat thyroid lesions II. An electron microscopic study. Acta Pathol Jpn 37:1441–1453
Kawaoi A, Moriyama S (1987c) Diisopropanolnitrosamine (DIPN) induced rat thyroid lesions III. An immunohistochemical study on their functional aspects. Acta Pathol Jpn 37:1455–1463
Kitahori Y, Hiasa Y, Konishi N, Enoki N, Shimoyama T, Miyashiro A (1984) Effect of propylthiouracil on the thyroid tumorigenesis induced by N-bis(2-hydroxypropyl) nitrosamine in rats. Carcinogenesis 5:657–660
Kuramoto S, Oohara T (1988) Minute cancers arising de novo in the human large intestine. Cancer 61:829–834
Lang W, Georgii A, Stauch G, Kienzle E (1980) The differentiation of atypical adenomas and encapsulated follicular carcinomas in the thyroid gland. Virchows Arch A Pathol Anat Histol 385:125–141
Maskens AP, Dujardin-Loits R-M (1981) Experimental adenomas and carcinomas of the large intestine behave as distinct entities: most carcinomas arise de novo in flat mucosa. Cancer 47:81–89
Moriyama S, Kawaoi A, Hirota N (1983) Gamma-glutamyl transpeptidase in putative precancerous thyroid lesions of rats treated with diisopropanolnitrosamine. Br J Cancer 47:299–301
Morstyn G, Hsu S-M, Kinsella T, Gratzner H, Russo A, Mitchell JB (1983) Bromodeoxyuridine in tumors and chromosomes detected with a monoclonal antibody. J Clin Invest 72:1844–1850
Nowell PC (1986) Mechanisms of tumor progression. Cancer Res 46:2203–2207
Peroino C, Staffeldt EF, Carnes BA, Ludeman VA, Blomquist JA, Vesselinovitch SD (1984) Characterization of histochemically detectable altered hepatocyte foci and their relationship to hepatic tumorigenesis in rats treated once with diethylnitrosamine or benzo(α)pyrene within one day after birth. Cancer Res 44:3340–3347
Pitot HC (1989) Progression: The terminal stage in carcinogenesis. Jpn J Cancer Res 80:599–607
Potter VR (1981) A new protocol and its rationale for the study of initiation and promotion of carcinogenesis in rat liver. Carcinogenesis 2:1375–1379
Reznic G (1977) Carcinogenic effect of diisopropanolnitrosamine on the rat thyroid gland. Verh Dtsch Ges Pathol 61:299–302
Robbins BA, dela Vega D, Ogata K, Tan EM, Nakamura RM (1987) Immunohistochemical detection of proliferating cell nuclear antigen in solid human malignancies. Arch Pathol Lab Med 111:841–845
Thomas C, Bollmann R (1974) Zur kausalen Pathogenese und Morphologie der Schilddrüsentumoren bei der Ratte. Z Krebsforsch 81:243–249
Tsuda H, Hananouchi M, Tatematsu M, Hirose M, Hirano K, Takahashi M, Ito N (1976) Tumorigenic effect of 3-amino-1H-1, 2,4-triazole on rat thyroid. J Natl Cancer Inst 57:861–864
Yamashita H, Nakayama I, Noguchi S, Murakami N, Moriuchi A, Yokoyama S, Mochizuki Y, Noguchi A (1985) Thyroid carcinoma in benign thyroid diseases. An analysis from minute carcinoma. Acta Pathol Jpn 35:781–788
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kawaoi, A., Matsumoto, H., Suzuki, K. et al. Histogenesis of diisopropanolnitrosamine (DIPN)-induced tumors of the rat thyroid gland. Virchows Archiv B Cell Pathol 61, 49–56 (1992). https://doi.org/10.1007/BF02890404
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02890404