Prostacyclin is a potent anti-mutagen

Abstract

Prostacyclin (PGI2) prevented genetic damage to the bone marrow cells of mice induced by gamma-radiation, benzo(a)pyrene(BP) and cis-platinum(cis-DDP). Carba-PGI2, an analogue of PGI2, was also effective against cis-DDP-induced mutagenicity. In a time-course study it was observed that the geno-protective action of PGI2, can last as long as 24 hr. 6-keto-PGF1 alpha, a major metabolite of PGI2 and c-AMP, a second messenger, were ineffective in bringing about this beneficial action. PGI2 did not influence free radical generation induced by phorbol myristate acetate in human peripheral leukocytes. This suggests that the genoprotective action of PGI2 is not mediated by its metabolite 6-keto-PGF1 alpha and the second messenger cyclic-AMP and is not due to any action on free radical generation. This geno-protective action of PGI2 would be futile if it interfered with the tumoricidal action of cis-DDP. It was observed that the cytotoxic action of cis-DDP against Meth-A tumor cells was not interfered with by PGI2 and carba-PGI2 both in vitro and in vivo. This description of the geno-protective action of PGI2 is important in the development of new strategies in cancer chemotherapy since, it is likely that anticancer drugs, at least cis-DDP can be given along with PGI2 to prevent genetic damage to normal cells without interfering with their tumoricidal action.