Redox-dependent toxicity of diepoxybutane and mitomycin C in sea urchin embryogenesis

The effects and mechanisms of action of diepoxybutane (DEB) and mitomycin C (MMC) were investigated on sea urchin embryogenesis, (Sphaerechinus granul aris and Paracentrotus lividus). DEB- and MMC-induced toxicity was evaluate d by means of selected end-points, including developmental defects, cytogen etic abnormalities and alterations in the redox status [oxygen-dependent to xicity, Mn-superoxide dismutase (MnSOD) and catalase activities and glutath ione (GSH) levels]. Both DEB and MMC exhibited developmental toxicity (at c oncentrations ranging from 3 x 10(-5) to 3 x 10(-4) M and 3 x 10(-6) to 3 x 10(-5) M, respectively) expressed as larval abnormalities, developmental a rrest and mortality, The developmental effects of both compounds were signi ficantly affected by oxygen at levels ranging from 5 to 40%. These results confirmed previous evidence for oxygen-dependent MMC toxicity and are the f irst report of oxygen dependence for DEB toxicity, Both DEB and MMC exerted significant cytogenetic abnormalities, including mitotoxicity and mitotic aberrations, but with different trends between the two chemicals, at the sa me concentrations as exerted developmental toxicity. The formation of react ive oxygen species was evaluated using: (i) luminol-dependent chemiluminesc ence (LDCL); (ii) reactions of the main antioxidant systems, such as GSH co ntent and MnSOD and catalase activities. The results point to clear-cut dif ferences in the effects induced by DEB and MMC, Thus, DEB suppressed GSH co ntent within the concentration range 10(-7)-3 x 10(-5) M, The activity of c atalase was stimulated at lower DEB levels (10(-7)-10(-6) M) and then decre ased at higher DEB concentrations (greater than or equal to 10(-5) M), Incr easing MMC concentrations induced LDCL and MnSOD activity (greater than or equal to 10(-6) M) greatly and modulated catalase activity (10(-7) - 10(-6) M), GSH levels were unaffected by MMC, The results suggest that oxidative stress contributes to the developmental and genotoxic effects of both toxin s studied, although through different mechanisms.