Prostacyclin is a potent anti-mutagen

Abstract

Prostacyclin (PGI 2) prevented genetic damage to the bone marrow cells of mice induced by gamma-radiation, benzo(a)pyrene(BP) and cis-platinum(cis-DDP). Carba-PGI 2, an analogue of PGI 2, was also effective against cis-DDP-induced mutagenicity. In a time-course study it was observed that the geno-protective action of PGI 2, can last as long as 24 hr. 6-keto-PGF 1α, a major metabolite of PGI 2 and c-AMP, a second messenger, were ineffective in bringing about this beneficial action. PGI 2 did not influence free radical generation induced by phorbol myristate acetate in human peripheral leukocytes. This suggests that the genoprotective action of PGI 2 is not mediated by its metabolite 6-keto-PGF 1α and the second messenger cyclic-AMP and is not due to any action on free radical generation. This geno-protective action of PGI 2 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 PGI 2 and carba-PGI 2 both in vitro and in vivo. This description of the geno-protective action of PGI 2 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 PGI 2 to prevent genetic damage to normal cells without interfering with their tumoricidal action.