Immunocytochemical and Morphological Evidence for the Origin of N-Nitrosomethylurea-induced and Naturally Occurring Primary Lung Tumors in F344/NCr Rats

Masato Ohshima, Jerrold M. Ward, Gurmukh Singh, Sikandar L. Katyal

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Naturally occurring and N-nitrosomethylurea-induced lung tumors were studied in male F344/NCr rats by sequential histological, electron microscopic, and immunohistochemical methods. Rats were given one injection at 6 weeks of age of N-nitroso-methylurea at a dosage level of 41.2 mg/kg body weight i.v. Groups of rats were sacrificed at 20, 33, and 52 weeks, while some were sacrificed while moribund. Nine lung tumors from aged F344/NCr male rats were also studied. For determining localization of pulmonary antigens, sections of lungs were stained by the avidin-biotin-peroxidase complex immunocytochemical technique using antibodies to rat surfactant apoprotein or rat Clara cell antigen. At 20 weeks, in rats receiving N-nitrosomethylurea, focal alveolar type II cell hyperplasia, adenoma in focal alveolar type II cell hyperplasia, and adenoma were found in 15 (100%), 1 (7%), and 2 (13%) of 15 rats, respectively. At 33 weeks, there were 19 rats (95%) with focal alveolar type II cell hyperplasias, 10 rats (50%) with adenoma in focal alveolar type II cell hyperplasia, and 2 rats (10%) with adenomas in 20 rats. In 53 rats allowed to live up to 52 weeks, there were 10 (19%) adenomas and 3 (6%) carcinomas, as well as 49 (92%) rats with focal hyperplasia and 31 (58%) with adenomas in focal type II cell hyperplasia. Rat surfactant apoprotein was found in the cytoplasm of normal alveolar type II cells and the majority of cells in focal alveolar type II cell hyperplasias, adenomas in hyperplastic lesions, adenomas, and carcinomas. The ultrastructure of these lesions supported immunocytochemical findings with evidence of lamellar bodies. All nine naturally occurring lung tumors studied contained rat surfactant apoprotein. Rat Clara cell antigen was found, however, only focally within one adenoma induced by n-nitrosomethylurea and one adenoma in a hyper-plasic lesion, and also focally in three neoplasms which occurred naturally. This study provided morphological, immunohistochemical, and ultrastructural evidence that the vast majority of N-nitrosomethylurea-induced and naturally occurring pulmonary neoplasms of F344 rats are alveolar type II cell adenomas and carcinomas and that a portion of these tumors arise within focal alveolar type II cell hyperplasias.

Original languageEnglish (US)
Pages (from-to)2785-2792
Number of pages8
JournalCancer Research
Volume45
Issue number6
StatePublished - Jun 1 1985

Fingerprint

Methylnitrosourea
Inbred F344 Rats
Alveolar Epithelial Cells
Adenoma
Lung
Hyperplasia
Neoplasms
Apoproteins
Surface-Active Agents
Carcinoma
Avidin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Immunocytochemical and Morphological Evidence for the Origin of N-Nitrosomethylurea-induced and Naturally Occurring Primary Lung Tumors in F344/NCr Rats. / Ohshima, Masato; Ward, Jerrold M.; Singh, Gurmukh; Katyal, Sikandar L.

In: Cancer Research, Vol. 45, No. 6, 01.06.1985, p. 2785-2792.

Research output: Contribution to journalArticle

@article{5f42b53ff60a4534b665e6c482d83fc9,
title = "Immunocytochemical and Morphological Evidence for the Origin of N-Nitrosomethylurea-induced and Naturally Occurring Primary Lung Tumors in F344/NCr Rats",
abstract = "Naturally occurring and N-nitrosomethylurea-induced lung tumors were studied in male F344/NCr rats by sequential histological, electron microscopic, and immunohistochemical methods. Rats were given one injection at 6 weeks of age of N-nitroso-methylurea at a dosage level of 41.2 mg/kg body weight i.v. Groups of rats were sacrificed at 20, 33, and 52 weeks, while some were sacrificed while moribund. Nine lung tumors from aged F344/NCr male rats were also studied. For determining localization of pulmonary antigens, sections of lungs were stained by the avidin-biotin-peroxidase complex immunocytochemical technique using antibodies to rat surfactant apoprotein or rat Clara cell antigen. At 20 weeks, in rats receiving N-nitrosomethylurea, focal alveolar type II cell hyperplasia, adenoma in focal alveolar type II cell hyperplasia, and adenoma were found in 15 (100{\%}), 1 (7{\%}), and 2 (13{\%}) of 15 rats, respectively. At 33 weeks, there were 19 rats (95{\%}) with focal alveolar type II cell hyperplasias, 10 rats (50{\%}) with adenoma in focal alveolar type II cell hyperplasia, and 2 rats (10{\%}) with adenomas in 20 rats. In 53 rats allowed to live up to 52 weeks, there were 10 (19{\%}) adenomas and 3 (6{\%}) carcinomas, as well as 49 (92{\%}) rats with focal hyperplasia and 31 (58{\%}) with adenomas in focal type II cell hyperplasia. Rat surfactant apoprotein was found in the cytoplasm of normal alveolar type II cells and the majority of cells in focal alveolar type II cell hyperplasias, adenomas in hyperplastic lesions, adenomas, and carcinomas. The ultrastructure of these lesions supported immunocytochemical findings with evidence of lamellar bodies. All nine naturally occurring lung tumors studied contained rat surfactant apoprotein. Rat Clara cell antigen was found, however, only focally within one adenoma induced by n-nitrosomethylurea and one adenoma in a hyper-plasic lesion, and also focally in three neoplasms which occurred naturally. This study provided morphological, immunohistochemical, and ultrastructural evidence that the vast majority of N-nitrosomethylurea-induced and naturally occurring pulmonary neoplasms of F344 rats are alveolar type II cell adenomas and carcinomas and that a portion of these tumors arise within focal alveolar type II cell hyperplasias.",
author = "Masato Ohshima and Ward, {Jerrold M.} and Gurmukh Singh and Katyal, {Sikandar L.}",
year = "1985",
month = "6",
day = "1",
language = "English (US)",
volume = "45",
pages = "2785--2792",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "6",

}

TY - JOUR

T1 - Immunocytochemical and Morphological Evidence for the Origin of N-Nitrosomethylurea-induced and Naturally Occurring Primary Lung Tumors in F344/NCr Rats

AU - Ohshima, Masato

AU - Ward, Jerrold M.

AU - Singh, Gurmukh

AU - Katyal, Sikandar L.

PY - 1985/6/1

Y1 - 1985/6/1

N2 - Naturally occurring and N-nitrosomethylurea-induced lung tumors were studied in male F344/NCr rats by sequential histological, electron microscopic, and immunohistochemical methods. Rats were given one injection at 6 weeks of age of N-nitroso-methylurea at a dosage level of 41.2 mg/kg body weight i.v. Groups of rats were sacrificed at 20, 33, and 52 weeks, while some were sacrificed while moribund. Nine lung tumors from aged F344/NCr male rats were also studied. For determining localization of pulmonary antigens, sections of lungs were stained by the avidin-biotin-peroxidase complex immunocytochemical technique using antibodies to rat surfactant apoprotein or rat Clara cell antigen. At 20 weeks, in rats receiving N-nitrosomethylurea, focal alveolar type II cell hyperplasia, adenoma in focal alveolar type II cell hyperplasia, and adenoma were found in 15 (100%), 1 (7%), and 2 (13%) of 15 rats, respectively. At 33 weeks, there were 19 rats (95%) with focal alveolar type II cell hyperplasias, 10 rats (50%) with adenoma in focal alveolar type II cell hyperplasia, and 2 rats (10%) with adenomas in 20 rats. In 53 rats allowed to live up to 52 weeks, there were 10 (19%) adenomas and 3 (6%) carcinomas, as well as 49 (92%) rats with focal hyperplasia and 31 (58%) with adenomas in focal type II cell hyperplasia. Rat surfactant apoprotein was found in the cytoplasm of normal alveolar type II cells and the majority of cells in focal alveolar type II cell hyperplasias, adenomas in hyperplastic lesions, adenomas, and carcinomas. The ultrastructure of these lesions supported immunocytochemical findings with evidence of lamellar bodies. All nine naturally occurring lung tumors studied contained rat surfactant apoprotein. Rat Clara cell antigen was found, however, only focally within one adenoma induced by n-nitrosomethylurea and one adenoma in a hyper-plasic lesion, and also focally in three neoplasms which occurred naturally. This study provided morphological, immunohistochemical, and ultrastructural evidence that the vast majority of N-nitrosomethylurea-induced and naturally occurring pulmonary neoplasms of F344 rats are alveolar type II cell adenomas and carcinomas and that a portion of these tumors arise within focal alveolar type II cell hyperplasias.

AB - Naturally occurring and N-nitrosomethylurea-induced lung tumors were studied in male F344/NCr rats by sequential histological, electron microscopic, and immunohistochemical methods. Rats were given one injection at 6 weeks of age of N-nitroso-methylurea at a dosage level of 41.2 mg/kg body weight i.v. Groups of rats were sacrificed at 20, 33, and 52 weeks, while some were sacrificed while moribund. Nine lung tumors from aged F344/NCr male rats were also studied. For determining localization of pulmonary antigens, sections of lungs were stained by the avidin-biotin-peroxidase complex immunocytochemical technique using antibodies to rat surfactant apoprotein or rat Clara cell antigen. At 20 weeks, in rats receiving N-nitrosomethylurea, focal alveolar type II cell hyperplasia, adenoma in focal alveolar type II cell hyperplasia, and adenoma were found in 15 (100%), 1 (7%), and 2 (13%) of 15 rats, respectively. At 33 weeks, there were 19 rats (95%) with focal alveolar type II cell hyperplasias, 10 rats (50%) with adenoma in focal alveolar type II cell hyperplasia, and 2 rats (10%) with adenomas in 20 rats. In 53 rats allowed to live up to 52 weeks, there were 10 (19%) adenomas and 3 (6%) carcinomas, as well as 49 (92%) rats with focal hyperplasia and 31 (58%) with adenomas in focal type II cell hyperplasia. Rat surfactant apoprotein was found in the cytoplasm of normal alveolar type II cells and the majority of cells in focal alveolar type II cell hyperplasias, adenomas in hyperplastic lesions, adenomas, and carcinomas. The ultrastructure of these lesions supported immunocytochemical findings with evidence of lamellar bodies. All nine naturally occurring lung tumors studied contained rat surfactant apoprotein. Rat Clara cell antigen was found, however, only focally within one adenoma induced by n-nitrosomethylurea and one adenoma in a hyper-plasic lesion, and also focally in three neoplasms which occurred naturally. This study provided morphological, immunohistochemical, and ultrastructural evidence that the vast majority of N-nitrosomethylurea-induced and naturally occurring pulmonary neoplasms of F344 rats are alveolar type II cell adenomas and carcinomas and that a portion of these tumors arise within focal alveolar type II cell hyperplasias.

UR - http://www.scopus.com/inward/record.url?scp=0022005890&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022005890&partnerID=8YFLogxK

M3 - Article

VL - 45

SP - 2785

EP - 2792

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 6

ER -