Diepoxybutane and mitomycin C toxicity is associated with the induction of oxidative DNA damage in sea urchin embryos.
Diepoxybutane (DEB)- and mitomycin C (MMC)-associated toxicity was investigated in embryos from the sea urchin (SU) species Sphaerechinus granularis. DEB- and MMC-induced toxicity resulted in S. granularis embryos and larvae at concentrations ranging 10(-5) to 10(-4) M DEB, and 3 x 10(-6) to 3 x 10(-5) M MMC, in terms of larval malformations, developmental arrest and mortality. The formation of DNA oxidative damage, 8-hydroxy-2'-deoxyguanosine (8-OHdG) was measured in DEB- and in MMC-exposed embryos (at gastrula stage). A dose-dependent increase in 8-OHdG levels was observed that was significantly correlated with DEB- and MMC-induced developmental defects. The results lend further support to the body of evidence associating both DEB and MMC toxicity with oxidative stress, including DNA oxidative damage.
Pagano
G
G
G. Pascale Foundation, Italian National Cancer Institute, Naples.
Degan
P
P
De Biase
A
A
Iaccarino
M
M
Warnau
M
M
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000014:Abnormalities, Drug-Induced; D000818:Animals; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000378:metabolism; D004852:Epoxy Compounds / Q000633:toxicity*; D016685:Mitomycin / Q000633:toxicity*; D009153:Mutagens / Q000633:toxicity*; D009924:Organ Culture Techniques; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D012617:Sea Urchins
D004852:Epoxy Compounds; D009153:Mutagens; D016685:Mitomycin; C007366:diepoxybutane; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine