Effect of the promoter 12-O-tetradecanolyphorbol-13- acetate on the evolution of carcinogen-altered cell populations in tracheas initiated with 7,12-dimethylbenz(a)anthracene
The aim of these studies was to investigate the effect(s) of the promoter 12-O-tetradecanoylphorbol-13- acetate (TPA) on the evolution of different types of 7,12-dimethylbenz(a)anthracene (DMBA)-initiated rat tracheal epithelial cells in vivo. In the present study, tracheal transplants were exposed in vivo to 35 ..mu..g DMBA for 2 weeks and subsequently to 100 ..mu..g TPA. Controls were exposed to DMBA alone, TPA alone, or blank pellets alone. Tracheal cells were harvested by enzymatic procedures at 0, 3, 6, 12, or 18 months after the end of exposure to DMBA and at the same time points after the beginning of exposure to TPA or control pellets and were assayed in vitro with the epithelial focus (EF) assay for the frequency of different types of EF-forming units. Control tracheas yielded <1 EF/10/sub 4/ viable cells harvested. Exposure to TPA alone did not increase the yield of EF, EF/sub s/, or EF/sub s,ag+/ above control levels. Carcinogen exposure resulted in a 6- to 20-fold increase in yield of EF, a 2- to 3-fold increase in EF/sub s/, and a greater than or equal to 15-fold increase in yield of EF/sub s,ag+/ above control levels. Neither the yield of EF nor the yield of EF/sub s/ was affected by subsequent TPA. In contrast, there was a marked effect of subsequent TPA exposure on the maintenance and size of the cell pool giving rise to anchorage-independent offspring (EF/sub s,ag+/). In summary, it appears that initiation can be viewed as a series of complex cellular changes. With time, some of these changes are reversible. Exposure to TPA of cell populations initiated with low doses of DMBA results in the persistence of altered cell populations in the intact tissue. Without TPA treatment, some phenotypically altered cells appear to revert to a more normal state and/or fail to replicate. 26 references, 1 figure, 1 table.
- Research Organization:
- Oak Ridge National Lab., TN
- DOE Contract Number:
- W-7405-ENG-26
- OSTI ID:
- 6168787
- Journal Information:
- Cancer Res.; (United States), Vol. 43
- Country of Publication:
- United States
- Language:
- English
Similar Records
Effect of carcinogen dose on the dynamics of neoplastic development in rat tracheal epithelium
Selection of carcinogen-altered rat tracheal epithelial cells preexposed to 7,12-dimethylbenz(a)anthracene by their loss of a need for pyruvate to survive in culture
Related Subjects
DIMETHYLBENZANTHRACENE
TOXICITY
TUMOR PROMOTERS
CARCINOGENS
EPITHELIUM
IN VIVO
PHORBOL ESTERS
RATS
TRACHEA
TRANSPLANTS
TUMOR CELLS
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
AROMATICS
BODY
CONDENSED AROMATICS
ESTERS
MAMMALS
ORGANIC COMPOUNDS
PROMOTERS
RESPIRATORY SYSTEM
RODENTS
TISSUES
VERTEBRATES
550200* - Biochemistry