Evidence for the multistep nature of in vitro human epithelial cell carcinogenesis
Abstract
In keeping with the multistep development of human cancer in vivo, a stepwise approach to neoplastic transformation in vitro presents a reasonable strategy. We have recently developed an in vitro multistep model suitable for the study of human epithelial cell carcinogenesis. Upon infection with the adenovirus 12-simian virus 40 hybrid virus, primary human epidermal keratinocytes acquired an indefinite life span in culture but did not undergo malignant conversion. Subsequent addition of Kirsten murine sarcoma virus and human ras oncogene or chemical carcinogens (N-methyl-N{prime}-nitro-N-nitrosoguanidine or 4-nitroquinoline 1-oxide) to these cells induced morphological alterations and the acquisition of neoplastic properties. Subsequently it was found that this line could be transformed neoplastically by a variety of retrovirus-containing H-ras, bas, fes, fms, erbB, and src oncogenes. In addition, we found that the immortalized human epidermal keratinocyte (RHEK-1) line can be transformed neoplastically by exposure to ionizing radiation. Thus, this in vitro system may be useful in studying the interaction of a variety of carcinogenic agents and human epithelial cells. These findings demonstrate the malignant transformation of human primary epithelial cells in culture by the combined action of viruses, oncogenes, chemical carcinogens, or X-ray irradiation and support a multistep process for neoplastic conversion.
- Authors:
-
- National Cancer Institute, Bethesda, MD (USA)
- Publication Date:
- OSTI Identifier:
- 6516718
- Resource Type:
- Journal Article
- Journal Name:
- Cancer Research; (USA)
- Additional Journal Information:
- Journal Volume: 50:17 Suppl; Journal ID: ISSN 0008-5472
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; ANIMAL CELLS; ONCOGENIC TRANSFORMATIONS; NITRO COMPOUNDS; CARCINOGENESIS; NITROSO COMPOUNDS; X RADIATION; EPITHELIUM; KERATIN; MAN; MICE; ONCOGENES; VIRUSES; ANIMAL TISSUES; ANIMALS; BODY; CELL TRANSFORMATIONS; ELECTROMAGNETIC RADIATION; GENES; IONIZING RADIATIONS; MAMMALS; MICROORGANISMS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; PARASITES; PATHOGENESIS; PRIMATES; PROTEINS; RADIATIONS; RODENTS; SCLEROPROTEINS; TISSUES; VERTEBRATES; 560300* - Chemicals Metabolism & Toxicology; 560120 - Radiation Effects on Biochemicals, Cells, & Tissue Culture
Citation Formats
Rhim, J S, Yoo, J H, Park, J H, Thraves, P, Salehi, Z, and Dritschilo, A. Evidence for the multistep nature of in vitro human epithelial cell carcinogenesis. United States: N. p., 1990.
Web.
Rhim, J S, Yoo, J H, Park, J H, Thraves, P, Salehi, Z, & Dritschilo, A. Evidence for the multistep nature of in vitro human epithelial cell carcinogenesis. United States.
Rhim, J S, Yoo, J H, Park, J H, Thraves, P, Salehi, Z, and Dritschilo, A. 1990.
"Evidence for the multistep nature of in vitro human epithelial cell carcinogenesis". United States.
@article{osti_6516718,
title = {Evidence for the multistep nature of in vitro human epithelial cell carcinogenesis},
author = {Rhim, J S and Yoo, J H and Park, J H and Thraves, P and Salehi, Z and Dritschilo, A},
abstractNote = {In keeping with the multistep development of human cancer in vivo, a stepwise approach to neoplastic transformation in vitro presents a reasonable strategy. We have recently developed an in vitro multistep model suitable for the study of human epithelial cell carcinogenesis. Upon infection with the adenovirus 12-simian virus 40 hybrid virus, primary human epidermal keratinocytes acquired an indefinite life span in culture but did not undergo malignant conversion. Subsequent addition of Kirsten murine sarcoma virus and human ras oncogene or chemical carcinogens (N-methyl-N{prime}-nitro-N-nitrosoguanidine or 4-nitroquinoline 1-oxide) to these cells induced morphological alterations and the acquisition of neoplastic properties. Subsequently it was found that this line could be transformed neoplastically by a variety of retrovirus-containing H-ras, bas, fes, fms, erbB, and src oncogenes. In addition, we found that the immortalized human epidermal keratinocyte (RHEK-1) line can be transformed neoplastically by exposure to ionizing radiation. Thus, this in vitro system may be useful in studying the interaction of a variety of carcinogenic agents and human epithelial cells. These findings demonstrate the malignant transformation of human primary epithelial cells in culture by the combined action of viruses, oncogenes, chemical carcinogens, or X-ray irradiation and support a multistep process for neoplastic conversion.},
doi = {},
url = {https://www.osti.gov/biblio/6516718},
journal = {Cancer Research; (USA)},
issn = {0008-5472},
number = ,
volume = 50:17 Suppl,
place = {United States},
year = {Sat Sep 01 00:00:00 EDT 1990},
month = {Sat Sep 01 00:00:00 EDT 1990}
}