Oncogenic transformation in epithelial cell lines derived from tracheal explants exposed in vitro to N-methyl-N'-nitro-N-nitrosoguanidine
Rat tracheal explants were exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a known potent carcinogen, for examination of oncogenic transformation in respiratory tract epithelium in vitro. Organ cultures were exposed for 6 h on days 3 and 6 of culture to 0, 0.001, 1.0, or 10.0 ..mu..g of MNNG per ml of medium. Primary epithelial cell cultures, derived from 25 of the 30 carcinogen-exposed explants, underwent a distinct morphological change after approximately 160 days of culture. Only after this change could primary cell cultures be subcultured into cell lines. No cell lines could be established from control tissue. Tumorigenicity of the cell lines was determined after approximately 10 to 20 passages by inoculation of 10/sup 6/ cells into the thighs of immunosuppressed isogeneic rats. The number of explants that yielded tumorigenic cell lines was 0, 5, 6, and 9, respectively, for groups of 10 exposed to the above MNNG concentrations. The average latency period between inoculation and tumor appearance also showed a dose response. It was significantly shorter for cell lines in the group receiving 10 ..mu..g MNNG per ml (59.8 +- 7.3 (S.E.) days) than for cell lines in the group receiving 0.001 ..mu..g MNNG per ml (125 +- 10.7 days). Either adenosquamous cell carcinomas or keratinizing squamous cell carcinomas were obtained from cell lines in all groups. Four cell lines in the group receiving 10 ..mu..g MNNG per ml and 2 cell lines in the group receiving 1 ..mu..g MNNG per ml formed tumors which metastasized to other organs. During culture in vitro, cell lines became increasingly malignant. This was demonstrated by inoculation of some of the cell lines at successive passages. In all cases, tumor incidence increased and the latency period decreased with increasing passage number.
- Research Organization:
- Oak Ridge National Lab., TN
- DOE Contract Number:
- W-7405-ENG-26
- OSTI ID:
- 6849827
- Journal Information:
- Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 39; ISSN CNREA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL TISSUES
ANIMALS
BODY
CARBONIC ACID DERIVATIVES
CARCINOGENESIS
CARCINOMAS
DISEASES
DOSE-RESPONSE RELATIONSHIPS
EPITHELIUM
GUANIDINES
IN VITRO
MAMMALS
MORPHOLOGICAL CHANGES
NEOPLASMS
NITROSO COMPOUNDS
ONCOGENIC TRANSFORMATIONS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATHOGENESIS
RATS
RESPIRATORY SYSTEM
RODENTS
TIME DEPENDENCE
TISSUE CULTURES
TISSUES
TOXICITY
TRACHEA
VERTEBRATES