Carcinogen-induced Mitochondrial DNA Damage in the In Ovo Model

After experimental exposure of turkey eggs in an in ovo model, the induction of preneoplastic liver lesions (Enzmann et al., 1992and 1995a) and alterations of the mitochondrial (mt) DNA of embryonic turkey livers (Enzmann et al., 1995b) could be demonstrated, showing the sensitivity and usefulness of this short-termed and inexpensive system for carcinogenicity testing. Chemically induced modification of mtDNA may be an important indicator of the carcinogenic potential of substances, as the mt genome may display a higher sensitivity to DNA damaging effects compared to nuclear DNA. To characterize mtDNA damages in ovo, application of diethylnitrosamine (DEN) was performed onto the chorioallantoic membrane (CAM) of the avian embryo. First, the distribution of a model substance after CAM application was measured by autoradiography. MtDNA damage after DEN exposure was demonstrated by gel electrophoresis of isolated mtDNA. Nitrosamine treatment induced a dose-dependent change of mtDNA conformation from supercoiled to relaxed shape, pointing to a possible induction of single-strand breaks.