Spontaneous acute tumor lysis syndrome as a cause of early deaths in short-term carcinogenicity studies using p53 +/- mice.

摘要: Acute tumor lysis syndrome (ATLS) is a potentially lethal condition precipitated by the massive release of intracellular components such as nucleic acids, potassium, and phosphorus, following rapid widespread cells. Herein, authors describe high incidence characteristic histopathologic lesions acute ATLS in p53-deficient mice used 2 short-term carcinogenicity studies. was frequent cause early death p53 þ/– these studies consistently associated with presence disseminated lymphoma leukemia. Although heavy burden leukemia were present all affected mice, absence other equally severe indicates that burdens are necessary but insufficient to mice. The hallmark findings microemboli composed nuclear cytoplasmic debris derived from lysed mechanical obstruction capillary beds appeared be proximate deaths Microemboli may contribute pathogenesis renal failure clinical signs species. Recognition laboratory animals critical intended evaluate efficacy and/or toxicity anticancer treatments, where due might otherwise attributed test article toxicity. Further on role elucidate pathogenetic mechanisms lead improved approaches management treatment this condition.