HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Isolation of mutant adrenocortical tumor cells resistant to cyclic nucleotides.

Abstract
A somatic cell genetic approach was used to study the role of cyclic nucleotides in adrenal steroidogenesis. 8-Bromoadenosine 3',5'-monophosphate (8BrcAMP) stimulated steroidogenesis (K'd=0.1 mM) in cultured mouse adrenocortical tumor cells (Clone Y1). In addition, 8BrcAMP inhibited Y1 cell growth and caused Y1 cell monolayers to assume a rounded morphology. As a consequence, 8BrcAMP (at concentrations greater than or equal to 0.4 mM) reduced the relative plating efficiency of Y1 cells to less than 10(-5). Y1 cells were mutagenized with ethyl methanesulfonate (300 microgram/ml) and grown in the presence of 0.4 mM 8BrcAMP. A surviving colony (8BrcAMPr-1) was shown to be resistant to growth inhibition (relative plating efficiency at 1.0 mM 8BrcAMP=50 percent)) and to morphological changes induced by 8BrcAMP. 8BrcAMPr-1 cells had diminished steroidogenic responses to cyclic nucleotides and to ACTH (less than or equal to 33 percent of maximum). In 8BrcAMP(R)-1 cells, adenylate cyclase activity remained responsive to ACTH, and cyclic AMP phosphodiesterase activity was not increased. These data suggest that 8BrcAMPr-1 cells are defective at a point common to cyclic AMP action on growth, morphology and steroidogenesis. The associated decrease in responsiveness of the steroidogenic pathway to ACTH suggests that ACTH-regulated steroidogenesis is via a cyclic nucleotide-mediated mechanism.
AuthorsB P Schimmer, J Tsao, M Knapp
JournalMolecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 8 Issue 2 Pg. 135-45 (Aug 1977) ISSN: 0303-7207 [Print] Ireland
PMID200506 (Publication Type: Journal Article)
Chemical References
  • DNA, Neoplasm
  • Steroids
  • Xanthines
  • Adrenocorticotropic Hormone
  • Cyclic AMP
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Adenylyl Cyclases
  • Bromine
Topics
  • 3',5'-Cyclic-AMP Phosphodiesterases (metabolism)
  • Adenylyl Cyclases (metabolism)
  • Adrenal Cortex Neoplasms (metabolism)
  • Adrenal Gland Neoplasms (metabolism)
  • Adrenocorticotropic Hormone (pharmacology)
  • Animals
  • Bromine
  • Cell Survival (drug effects)
  • Cells, Cultured
  • Cyclic AMP (pharmacology)
  • DNA, Neoplasm (metabolism)
  • Drug Resistance
  • Mice
  • Mutation
  • Steroids (biosynthesis)
  • Xanthines (pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: