Enhanced sensitivity of the C3H/10T1/2 cell transformation system to alkylating and chemotherapeutic agents by treatment with 12-O-tetradecanoylphorbol-13-acetate

Journal Article · Sat Dec 31 23:00:00 EST 1983 · Environ. Mutagen.; (United States)

DOI:https://doi.org/10.1002/em.2860060110· OSTI ID:6577960

Frazelle, J H; Abernethy, D J; Boreiko, C J

The failure of the C3H/10T1/2 cell transformation system to respond to numerous known carcinogens has limited its applications for the detection and study of cancer-causing substances. Recent studies have found, however, that some carcinogens function as initiating agents for the process of transformation in these cells. Treatment with such agents is generally not sufficient to transform low-density asynchronous cultures of C3H/10T1/2 cells, but morphologic transformation will occur if such cultures are subsequently exposed to the potent tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). In the present study, the ability of TPA to enhance transformation was examined in cultures treated with a variety of chemical agents. The addition of TPA after chemical treatment enhanced the transformation of these cells by methylmethanesulfonate, ethylmethanesulfonate N-methyl-N'-nitro-N-nitrosoguanidine, N-nitrosomethylurea, N-nitrosoethylurea, mitomycin C, 5-fluorodeoxyuridine, and 5-azacytidine. Treatment with ameohopterin or benzo(e)pyrene did not produce significant numbers of foci in the presence or absence of TPA. TPA inhibited transformation by high concentrations of 3-methylcholanthrene and benzo(a)pyrene. Thus, numerous carcinogens function as initiating agents for these cells and the presence of TPA can dramatically increase the sensitivity of this cell transformation system.

• Research Organization: Chemical Industry Inst. of Toxicology, Research Triangle Park, NC
• OSTI ID: 6577960
• Journal Information: Environ. Mutagen.; (United States), Journal Name: Environ. Mutagen.; (United States) Vol. 6:1; ISSN ENMUD
• Country of Publication: United States
• Language: English

Related Subjects

560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
ANIMAL CELLS
ANIMALS
ANTINEOPLASTIC DRUGS
AROMATICS
AUGMENTATION
BENZOPYRENE
BIOLOGICAL EFFECTS
CARCINOGENS
CONDENSED AROMATICS
CONNECTIVE TISSUE CELLS
DRUGS
ESTERS
FIBROBLASTS
HYDROCARBONS
MAMMALS
MICE
NITROSAMINES
NITROSO COMPOUNDS
NITROSOUREAS
ONCOGENIC TRANSFORMATIONS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PHORBOL ESTERS
RESPONSE MODIFYING FACTORS
RODENTS
SENSITIVITY
SOMATIC CELLS
SULFONIC ACID ESTERS
VERTEBRATES