Ultrastructure of doxorubicin (adriamycin)-induced skin ulcers in rats.
Skin necrosis was produced in 24 male Fischer 344 rats by intradermal injection of 0.5 ml of doxorubicin (Adriamycin) at a concentration of 2 mg/ml. The resulting wounds healed slowly over 6 to 7 weeks with the reduced contraction rate paralleling the prolonged morbidity of doxorubicin ulcers in humans. Electron microscopy showed bizarre rough endoplasmic reticulum, double-walled  vacuoles, and swollen mitochondria from 1 through 12 weeks after injury. Myofibroblasts with 60- to 80-A microfilaments with electron-dense bodies, intercellular connections, and prominent microtubules were seen from 4 through 12 weeks after injury. Although the appearance of myofibroblasts was delayed, their structure was normal. The delayed contraction of doxorubicin-induced skin ulcers thus appears due to persistent nonspecific cellular damage at the nuclear level rather than to specific derangement of myofibroblast function.
D000818:Animals; D004317:Doxorubicin / Q000009:adverse effects*; D004721:Endoplasmic Reticulum / Q000648:ultrastructure; D008297:Male; D008933:Mitochondrial Swelling; D009210:Myofibrils / Q000648:ultrastructure; D009336:Necrosis / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D012883:Skin Ulcer / Q000139:chemically induced* / Q000473:pathology; D013997:Time Factors; D014945:Wound Healing
D004317:Doxorubicin