In vitro development of oncogenicity in cell lines established from tracheal epithelium preexposed in vivo to 7,12-dimethylbenz(a)anthracene
The purpose of these studies was to determine whether carcinogenesis initiated in vivo in tracheal epithelium of rats progresses in vitro. Transplanted rat tracheas were exposed to either 150 or 640 ..mu..g of 7,12-dimethylbenz(a)anthracene over a period of 2 weeks. Epithelial cell lines were derived from these tracheas and were tested periodically in vivo for development of oncogenicity and for phenotypic changes associated with neoplastic transformation in vitro. Three cell lines were obtained from tracheas preexposed to 150 ..mu..g 7,12-dimethylbenz(a)anthracene. Tumorigenicity was demonstrated only in the late passages of 2 cell lines maintained to 400 days or more in vitro. With these cells in vivo tumor latency was 115 to 255 days. Eight of the 9 cell lines derived from tracheas preexposed to 640 ..mu..g 7,12-dimethylbenz(a)anthracene became tumorigenic. Several of these were found to be oncogenic after approximately 200 days in vitro and yielded palpable tumors within 9 to 80 days after inoculation. In several instances inoculation of cells from early passage into immunosuppressed isogenic recipients resulted in the development of keratinic cysts or tumors that regressed. Inoculation of later passages of the same cell lines resulted in the development of invasive tumors. Loss of anchorage dependence of growth was, in most cases, a reliable phenotypic marker for development of oncogenicity, as was colony-forming efficiency on plastic. All of the cell lines were epithelial as indicated by ultrastructural characteristics, the production of keratin in vitro, and/or the formation of squamous cell carcinomas upon inoculation in vivo. The cell lines had stable morphological characteristics. Data indicate that the process of carcinogenesis initiated in epithelial cells in vivo continues in in vitro culture.
- Research Organization:
- Oak Ridge National Lab., TN
- OSTI ID:
- 6040837
- Journal Information:
- Cancer Res.; (United States), Vol. 38
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
CELL CULTURES
CARCINOGENESIS
ONCOGENIC TRANSFORMATIONS
DIMETHYLBENZANTHRACENE
CFU
EPITHELIUM
EXPERIMENTAL NEOPLASMS
IN VITRO
IN VIVO
MORPHOLOGY
NEOPLASMS
RATS
TRACHEA
ANIMALS
AROMATICS
BODY
CONDENSED AROMATICS
DISEASES
MAMMALS
ORGANIC COMPOUNDS
PATHOGENESIS
RESPIRATORY SYSTEM
RODENTS
TISSUES
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)
560301 - Chemicals Metabolism & Toxicology- Cells- (-1987)
550300 - Cytology