Increased cyclic AMP content directly correlated with morphological transformation of cells infected with a temperature-sensitive mutant of mouse sarcoma virus.
Normal rat kidney cells infected with a cold-sensitive mutant of mouse sarcoma virus [NRK(MSV-lb)] morphologically transform when exposed to adenosine 3':5' cyclic monophosphate (cAMP) at the restrictive temperature. The cAMP-induced morphological changes occur rapidly and are reversible. Agents capable of elevating endogenous levels of cAMP [prostaglandin E1 (PGE1) and cholera toxin (CT)] induced morphological transformation of NRK(MSV-lb) cells at the restrictive temperature that was concentration dependent, potentiated by cAMP phosphodiesterase inhibitors, and not prevented by inhibitors of DNA, RNA, and protein synthesis. Prostaglandin E1 stimulated a transient increase in the intracellular level of cAMP with a concomitant morphological transformation and reversion of cells as cAMP levels decline. The maximum increase is reached by 10 min, followed by a decline to near basal level by 80 min. In contrast, incubation of cells with CT resulted in irreversible morphological transformation and increased levels of cAMP first detectable by 1 hr with maximum levels reached by 24 hr. Heated CT (100 degrees C, 20 min) was without effect. Addition of CT to reverted PGE1-treated cells resulted in morphological transformation suggesting the existence of discrete receptors in NRK(MSV-lb) cells.
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D009053:Sarcoma Viruses, Murine / Q000502:physiology*; D013696:Temperature
D011458:Prostaglandins E; D002772:Cholera Toxin; D000242:Cyclic AMP