COMPARATIVE EMBRYOTOXICITY OF 4 ANTHRACYCLINES - IN-VITRO STUDY ON THEIR EFFECTS ON GLUTATHIONE STATUS

The embryotoxicity of four different anthracyclines [doxorubicin (DOXO ), epirubicin (EPI), daunorubicin (DAUNO) and idarubicin (IDA)] was co mpared using the postimplantation whole embryo culture method. Moreove r, to investigate the role of free oxygen radical production in anthra cpcline-induced embryotoxicity, the reduced glutathione (GSH) status i n embryos and extraembryonic membranes was measured. Rat embryos (1-3 somite stage) were cultured for 48 hr in heat-inactivated rat serum co ntaining DOXO, EPI or DAUNO (0.025, 0.05, 0.075 or 0.1 mu M) or IDA (0 .0125, 0.025 or 0.05 mu M). At the end of the culture period, the embr yos were examined morphologically and processed for histological or bi ochemical examination. DOXO, EPI and DAUNO were found to have similar embryotoxic potential [the no-observed-effect level (NOEL) was 0.025 m u M], whereas IDA had a greater effect (NOEL = 0.0125 mu M). The prima ry target organ was identified macroscopically and microscopically for all compounds in the mesenchyme of the caudal region. No relationship was identified between embryonic or extraembryonic GSH content reduct ion and anthracycline-induced embryotoxicity, suggesting only a margin al role of free oxygen radical formation in anthracycline-related embr yotoxic mechanisms. (C) 1997 Elsevier Science Ltd.