Role of cAMP and cGMP in the onset and release of radiation-induced mitotic delay (RIMD)

Previous studies with a mitotically synchronous slime mold have shown that γ-radiation rapidly induces a transient increase in cellular cAMP followed by a G/sub 2/-M delay. Subsequent autonomous or caffeine (Cf)-accelerated recovery from RIMD is temporally associated with a transient increase in cellular cGMP. Continuing studies with the L5178Y mouse lymphoma employing exogenous CNs and phosphodiesterase inhibitors have extended these findings showing that dibutyryl cGMP (DBcGMP) or Cf accelerates temporal recovery from RIMD whereas dibutryl cAMP (DBcAMP) and drugs enhancing cellular cAMP retard recovery. In S-49w mouse lymphoma cells, added cAMP, DBcAMP or Cf enhances RIMD, while DBcGMP has no effect indicating defective Cf- and cG-mediated recovery from RIMD. Although the cAMP content of various cell types can be variously regulated, the cyclo-oxygenase (CO) and lipoxygenase (LO) pathways have been reported to regulate cAMP and CGMP, respectively. Indomethicin (Ind) (30 60 μM), a CO inhibitor, strongly enhances RIMD (4 Gy) recovery. Eicosatetraynoic acid (100 μM), inhibiting both CO and LO, allows partial recovery, possibly reflecting inhibition of both a cAMP-controlling (CO) and a cGMP-controlling (LO) pathway