Liver tumor promoting effect of etofenprox in rats and its possible mechanism of action.

To investigate the liver tumor-promoting effects of etofenprox (ETF), a pyrethroid-like insecticide, 6 week-old male F344 rats were given an intraperitoneal injection of N-diethylnitrosamine (DEN). After 2 weeks from the DEN treatment, 12 rats per group received a powdered diet containing 0, 0.25, 0.50, or 1.0% ETF for 8 weeks. At the time of 2nd week of ETF administration, all animals were subjected to two-thirds partial hepatectomy (PH). One rat per group except for the 0.25% ETF group died due to surgical operation of PH. The number and area of glutathione S-transferase placental form (GST-P) positive foci significantly increased in the livers of DEN-initiated rats given 0.50% and 1.0% ETF compared with the DEN-alone group. Quantitative real-time RT-PCR analysis revealed that the mRNA expression of phase I enzymes Cyp2b1/2, phase II enzymes such as Akr7a3, Gsta5, Ugt1a6, Nqo1 significantly increased in the DEN+ETF groups. The immunohistochemistry showed the translocation of CAR from the cytoplasm to the nuclei of hepatocytes in the ETF-treated groups. Reactive oxygen species (ROS) production increased in microsomes isolated from the livers of ETF-treated rats, and thiobarbituric acid-reactive substances (TBARS) levels and 8- hydroxy-2-deoxyguanosine (8-OHdG) content significantly increased in all of the ETF-treated groups and DEN+1.0% ETF group, respectively. The results of the present study indicate that ETF has a liver tumor-promoting activity in rats, and suggest that ETF activates the constitutive active/androstane receptor (CAR) and enhances microsomal ROS production, resulting in the upregulation of Nrf2 gene batteries; such an oxidative stress subsequently induces liver tumor-promoting effects by increased cellular proliferation.

Complex apocrine carcinoma with dominant myoepithelial proliferation in a dog.

A rare case of complex apocrine carcinoma displaying dominant myoepithelial proliferation developed in the right leg subcutis of a 10-year-old male dog. The major cell population consisted of diffusely proliferating p63-expressing neoplastic cells that were largely myoepithelial in origin co-expressing α-smooth muscle actin. A small portion of the cell population consisted of concomitant basal epithelial cells lacking α-smooth muscle actin expression. The minor population consisted of p63-negative apocrine gland cells that expressed cytokeratin 8. The myoepithelial cell population showed a rather stronger proliferation activity than did the apocrine epithelial population. Thus, this tumor might have been derived from basal epithelial cells characterized by more predominant myoepithelial differentiation than luminal apocrine epithelial differentiation.

High-grade myofibroblastic sarcoma of inguinal region in a dog.

A subcutaneous tumor in the left inguinal region was present in an 11-year-old female bloodhound. Histopathologically, the tumor showed invasive growth and extensive necroses, and it was composed of spindle-shaped, elongated, and stellate neoplastic cells accompanied by occasional giant cells arranged in fascicular, herringbone, or irregular storiform patterns with abundant production of collagen fibers. The cytoplasm of most tumor cells was positive for vimentin, alpha-smooth muscle actin, and calponin, but was negative for desmin, smoothelin, and S-100. Furthermore, most of the tumor cells were negative for Iba1 while some tumor cells were weakly positive. Thus, this tumor was diagnosed as a high-grade myofibroblastic sarcoma according to the diagnostic criteria for human myofibroblastic sarcomas.