Diethylnitrosamine (DEN) induced morphological and biomolecular changes in mouse liver mitochondria

Liver contains substantial numbers of mitochondria (1000-2000 per cell) making up 1/5th of the cell volume. In addition to supplying cellular energy, mitochondria are involved in various other processes, such as signaling, cellular differentiation, cell death (apoptosis) and in the control of the cell cycle and cell growth. Diethylnitrosamine (DEN) is a complete carcinogen, known to induce liver carcinogenesis in experimental animal models. In the present study, we assessed the effects of DEN on liver mitochondria. DEN (10 mg/kg body wt.) was administered to mice by I.V. Route at weekly intervals for up to16 weeks. Carcinogenesis response modulation induced in experimental mice was followed by liver marker enzyme assays such as gamma glutamyl transpeptidase (GGT), acetylcholine esterase (AChE) and glutathione S-transferase (GST) along with the histological examination and transmission electron microscopy (TEM) study of the liver tissues as well. Morphological and molecular alterations in the mitochondrial membrane were studied in isolated mitochondria obtained from the liver tissues of DEN-treated mice. Significant changes were observed in the morphology of mitochondrion upon DEN treatment compared to the standard control. Alterations were also seen in cardiolipin (CL) content, one of the three major phospholipids present in the inner mitochondrial membrane, and also in the expression level of mitochondria membrane surface protein(s) in DEN-treated mice. Alterations in morphology, CL content and differential expression of membrane surface proteins may be associated with mitochondrial dysfunction in the liver and involved in the pathology of cancer.