Evidence for the multistep nature of in vitro human epithelial cell carcinogenesis
- National Cancer Institute, Bethesda, MD (USA)
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.
- OSTI ID:
- 6516718
- Journal Information:
- Cancer Research; (USA), Vol. 50:17 Suppl; ISSN 0008-5472
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
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