title: Leukocyte response to toxic injury.
abstract: Exposure to a variety of drugs and toxins can induce hematopoietic damage. These agents exert their effects through several distinct mechanisms including destruction or suppression of hematopoietic stem cells, cytotoxic destruction of rapidly proliferating precursor cells, immune-mediated hematotoxicity, altered hematopoietic microenvironment, genetic mutation, and microvascular injury. Some toxins consistently produce suppression of granulopoiesis in a dose-dependent manner, whereas others produce idiosyncratic reactions. Although all types of injury tend to result in granulocytopenia, the time course of the changes varies with the type of injury. With acute destruction of the proliferative pool of granulocytes, neutropenia develops within 7 days and recovery occurs within days after discontinuing treatment. With stem cell injury, the onset of hematotoxicity is variable and damage is often permanent. Immune-mediated reactions may occur acutely or after months or years of treatment with a drug. Drugs or toxins that act as mutagens can induce a variety of hematopoietic disorders including aplastic anemia, myelodysplasia, and leukemia. Therefore, the time course of onset of leukopenia after drug or chemical exposure and the rapidity of hematopoietic recovery give clues to the mechanism by which granulopoiesis is suppressed.
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Minnesota, St. Paul 55108.
authors.forename: D J
authors.initials: DJ
authors.lastname: Weiss
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D064420:Drug-Related Side Effects and Adverse Reactions; D004967:Estrogens / Q000633:toxicity; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects*; D009503:Neutropenia / Q000139:chemically induced; D013449:Sulfonamides / Q000633:toxicity
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004967:Estrogens; D013449:Sulfonamides