N-acetyl cysteine provides partial protection against TCDD-induced lethality in fish embryos

Cellular oxidative damage is induced by a wide variety of environmental factors including UV-irradiation and xenobiotics. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), the prototypical xenobiotic, has been shown to induce cellular oxidative damage in the adult rat (Stohs et al, 1990). The measured endpoints of TCDD-induced oxidative damage in the rat include: membrane lipid oxidation, DNA damage and protein alterations. We have tested the hypothesis that TCDD-induced oxidative damage is responsible for the observed lethality after TCDD exposure both in vitro (a fish cell line, PLHC-1) and in vivo (fish embryos, Oryzias latipes). To examine the role that cellular oxidative damage plays in TCDD-induced lethality, we tested the ability of an anti-oxidant to provide protection from TCDDʹs lethal effects. In the TCDD-treated fish cells and fish embryos, an anti-oxidant was able to provide partial protection from lethality, indicating that TCDD induces cellular oxidative damage. These data suggest that TCDD-induced cellular oxidative damage plays a role in the toxic manifestation of TCDD in the developing fish embryo.