Control Id: 152096

BODY: Hemangiosarcoma is an aggressive, malignant tumor of endothelial cells that is rare in humans. In the 12 regions of the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database, the incidence rate of hemangiosarcoma between 1996 and 2000 was 0.21 new cases per 100,000 people (0.00021%). Hemangiosarcoma in humans commonly occurs on head and neck and is associated with skin structures. Liver hemangiosarcoma is associated with exposure to genotoxic compounds such as Thorotrast or vinyl chloride. In contrast, hemangiosarcoma occurs spontaneously in liver, spleen, bone marrow, lymph nodes and skin at a high incidence in rodents. The background incidence in B6C3F1 mice reported from the National Toxicology Program database is 5.4% in males and 2.7% in females with a range from 0% to 12%. The incidence in Wistar rats ranges from 0 3.4 %. These data suggest that mice are more susceptible to development of spontaneous hemangiosarcoma than rats and much more susceptible than humans. Hemangiosarcoma in rodents, primarily mice, has been reported in the labeling of a number of marketed drug products and in the literature with several chemicals. Some of these compounds demonstrated genotoxic potential in nonclinical testing and thus a plausible mechanism for tumor induction. Others, however, are clearly nongenotoxic and a mode of action is more difficult to establish. Regardless, findings of hemangiosarcoma have significant impact on decisions made regarding further development of these agents and future usage. Recent research has provided a great deal of information on epigenetic mechanisms of tumorigenesis relating to these compounds. Species differences in hemangiosarcoma incidence may be related to factors responsible for normal endothelial homeostasis and thus provide a basis for risk assessment. This symposium will focus on characterization of unique biological aspects of hemangiosarcoma, current issues and impact on drug and chemical development, and case studies describing recent research on tumorigenic mechanisms with relevance to human risk