2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine is a heterocyclic aromatic amine found in cooked meats and dietary exposure to PhIP has been implicated in the etiology of colon cancer in humans. PhIP, along with other heterocyclic aromatic amines, requires metabolic activation to exhibit genotoxic effects. PhIP is initially oxidized by the activity of cytochrome P4501A2 to produce 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP), a reaction occurring primarily in the liver. Whereas subsequent biotransformation of N-OH-PhIP via acetylation or sulfation can produce reactive electrophiles that readily bind to DNA, N-glucuronidation, catalyzed by UDP-glucuronosyltransferases (UGTs), functions as a detoxification mechanism. Although hepatic glucuronidation of N-OH-PhIP has been well characterized, the extrahepatic metabolism of this compound is poorly understood. Studies in our laboratory now indicate that the intestinal tract, and particularly the colon, is a significant site of glucuronidation of N-OH-PhIP. When assays were performed with microsomes prepared from the mucosa of the intestinal tract, it was determined that glucuronidation of N-OH-PhIP occurs throughout the intestinal tract, with activity approximately three times higher in the colon as that found in the upper intestine. Glucuronidation rates from colon microsomes showed considerable interindividual variability and incubation with N-OH-PhIP yielded two glucuronides. HPLC analysis showed that the predominant product formed is the N-OH-PhIP-N2-glucuronide, while the N3-glucuronide accounts for <10% of the total glucuronidation product. These rates approach the rates found in human liver microsomes, demonstrating the significance of extrahepatic metabolism of this food-borne carcinogen. Subsequent assays with human recombinant UGTs demonstrated that at least four human UGT isoforms, all from the UGT1A subfamily, are capable of catalyzing the biotransformation of N-OH-PhIP. Members of the UGT2B family available for this study did not conjugate N-OH-PhIP, although immunoinhibition studies in human liver microsomes strongly suggest the involvement of a UGT2B isoform(s) in this organ.

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ABSTRACT. In the 3 years leading up to November 2009, 6 different types of naturally occurring neoplasms associated with avian leukosis virus subgroup J (ALV-J) were diagnosed by histopathology, polymerase chain reaction (PCR) and immunohistochemistry (IHC) in 140 layer hens out of approximately 100,000. The most prevalent tumor type was hemangioma (50%) in commercial layer flocks; the second most prevalent neoplasm type was myelocytoma (38.6%); a small number of ALV-J positive lymphomas (4.3%) that were not associated with Marek's disease (MD) or lymphoid leukosis (LL) was observed. Histiocytic sarcomas (2.1%) were found mainly in the spleen, liver and kidney. Fibrosarcomas (2.8%) presented as metastatic thigh, liver, lung and kidney neoplasms. Three cases of intestinal adenocarcinoma (2.1%) were found associated with ALV-J. Chickens with multiple tumors were a common phenomenon. Usually, hemangiomas plus myelocytomas (8.6%), myelocytomas plus histiocytic sarcomas (2.1%), hemangioma plus myelocytoma and lymphoma (3.6%) were found in various viscera organs. The present report describes the occurrence of multiple neoplasms associated with ALV-J in field layer hens.KEY WORDS: avian leukosis virus subgroup J (ALV-J), layer chickens, multiple neoplasms.J. Vet. Med. Sci. 72(8): 1027-1033, 2010 Avian leukosis virus subgroup J (ALV-J), first described in the United Kingdom in 1991 and later in other countries, has been associated primarily with myeloid leukosis in meat-type chickens [8,[11][12][13][14][15]. ALV-J has caused severe economic losses in broiler breeders throughout the world. Vertical transmission from broiler breeders to progeny is more frequent with ALV-J than with other ALV subgroups [25].ALV-J in the field has occurred almost entirely in meattype chickens several years ago. Layers have rarely become infected, but experimental studies with Rous sarcoma virus having the inserted envelope gene of ALV-J by Payne [16] have shown that both layers and turkeys are susceptible to ALV-J infection, while other poultry and game birds appear to be resistant.The frequencies of different tumor types seen by Payne [11] during 1996-1998 from suspect ALV-J infected flocks were 58% for myeloid leukosis (ML), 12% for histiocytic sarcoma (HS), 9% for erythroblastosis and 5% for blast cell tumors. Numerous birds had more than one type of tumor, and some had up to four different types.In chickens, layer strains are considered to be at risk in China and their exposure to ALV-J contamination has already been demonstrated by Xu [23,24,26] and Cheng [6]. ALV-J in egg-type chickens with ML has already resulted in significant economic losses in China. Gingerich [9] also reported that a recombinant ALV containing the long terminal repeat (LTR) of the subgroup J and the envelope of subgroup B was isolated from commercial White Leghorn flocks with ML. Cheng [5] reported cases of ML diagnosed in a local Chinese breed that is commonly recognized as a dual purpose type of chicken, both for eggs and meat, in Shandong Province, P.R. China....

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Pseudorabies virus (PRV) infects numerous species of domestic and wild animals leading to severe diseases especially in swine and cattle. Since 2011, the variant PRVs were identified in pigs, which were genetically different from classic strains. Although variant PRV infection is widely observed in pigs, there is still no report of variant PRV infection in cattle. Here, we reported a natural infection of variant PRV leading to acute bovine death in Eastern China. Our study suggests that the new variant PRV strains could be a potential threat to cattle industry and possibly to the public health of human.

p60 is a subunit of katanin involved in microtubule-severing. Previous studies of p60 were primarily focused on microtubule regulation and cell cycle regulation. More recent research has demonstrated that katanin p60 possesses a function in prostate cancer bone metastasis; however, its role in breast cancer bone metastasis remains unclear. In the present study, immunohistochemistry was used to analyze the expression of katanin p60 in primary and bone metastatic breast cancer. The role of up- and downregulated katanin p60 was investigated using cell proliferation, and migration experiments. Overall, katanin p60 was highly expressed in breast cancer bone metastatic tissue compared with primary tumor tissue. In breast cancer cells, overexpression of katanin p60 inhibited cell proliferation, but promoted cell migration, whereas silencing katanin p60 expression promoted cell proliferation but inhibited cell migration. Overall, the present study indicated that katanin p60 serves a role in cell proliferation and migration, and thus may be a novel therapeutic target for prevention of breast cancer metastasis.