Cytotoxic effects of 6-mercaptopurine on the limb-bud blastemal cells of rat embryos.
On day 12 of pregnancy Wistar rats were each given a single ip injection of 5, 8, 16, 25, or 50 mg/kg 6-mercaptopurine. The embryos were removed 1, 2, 3, 5, 6, 10, 24, 48, or 72 h after injection or on day 20 and studied by light and electron microscopy. After 25 or 50 mg/kg all embryos showed no mineralization in the lower extremities. By electron microscopy condensation, shrinking, and fragmentation of cells in the limb bud blastema could be seen after 5 h. The fragments were phagocytosed and broken down by neighboring cells or remained in the extracellular space. After 25 or 50 mg/kg the damage was so extensive that the number of undamaged cells and of cells transforming into phagocytes was not sufficient to remove the debris or to compensate for the defect by mitotic activity. Epithelial cells, nerves, and blood vessels, show no morphological signs of damage. The "critical period" was the time cartilage just starts developing, i.e., when the blastema begins to differentiate.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects; D005121:Extremities / Q000196:embryology* / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D015122:Mercaptopurine / Q000633:toxicity*; D051379:Mice; D008854:Microscopy, Electron; D009336:Necrosis / Q000139:chemically induced; D010586:Phagocytes / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D011247:Pregnancy; D013997:Time Factors
D000970:Antineoplastic Agents; D015122:Mercaptopurine