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Mouse 3T3-L1 cell variants unable to respond to mitogenic stimulation of dihydroteleocidin B: genetic evidence for the synergism of tumor promoters with growth factors

Journal Article · · Cancer Res.; (United States)
OSTI ID:5117584
; ; ;

Dihydroteleocidin B, an indole alkaloid tumor promoter, stimulates confluent, quiescent mouse 3T3-L1 fibroblasts to initiate DNA synthesis and undergo cell division. Using a mitotic shakeoff technique, we have isolated 12 clones of genetic variants which are unable to respond to the mitogenic stimulation of dihydroteleocidin B from a total of 12 million cells. Biochemical characterization of these nonresponsive variants to dihydroteleocidin B revealed that there is no change in the ability to bind (/sup 3/H)phorbol dibutyrate, the activity of protein kinase C, and the turnover of phosphatidylinositol. The evidence indicates that nonresponsiveness to dihydroteleocidin B is caused by several different lesions, including defects in receptors for insulin or epidermal growth factor and in the postreceptor mechanisms. The evidence also suggests that mitogenic signal transfer via the epidermal growth factor receptor system appears to share a common step with dihydroteleocidin B whereas the signal transfer for insulin seems separate from these. These results suggest that phosphatidylinositol turnover followed by protein kinase C activation alone is not sufficient for mitogenic stimulation and that the coordination of the protein kinase C system with the receptor systems for growth factors may be necessary for ''full'' mitogenic response.

Research Organization:
Univ. of Arizona, Tucson
OSTI ID:
5117584
Journal Information:
Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 8; ISSN CNREA
Country of Publication:
United States
Language:
English

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Related Subjects

560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
AROMATICS
AZAARENES
AZOLES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARCINOGENS
CELL CULTURES
CELL DIVISION
CHEMICAL REACTIONS
CLONE CELLS
CONNECTIVE TISSUE CELLS
DNA
ENZYMES
ESTERS
FIBROBLASTS
GROWTH
HETEROCYCLIC COMPOUNDS
HISTONES
HORMONES
HYDROGEN ISOTOPES
INDOLES
INSULIN
ISOTOPES
LIGHT NUCLEI
MAMMALS
MICE
MITOGENS
NUCLEI
NUCLEIC ACIDS
NUCLEOPROTEINS
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDE HORMONES
PHORBOL ESTERS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHORYLATION
PHOSPHOTRANSFERASES
PROMOTERS
PROTEINS
PYRROLES
RADIOISOTOPES
RODENTS
SOMATIC CELLS
STIMULATION
SYNERGISM
TOXICITY
TRANSFERASES
TRITIUM
TUMOR PROMOTERS
VERTEBRATES
YEARS LIVING RADIOISOTOPES