Pathological effects of bleomycin on the skin of dogs and monkeys

Abstract

Bleomycin, an antitumor antibiotic with specific activity against squamous cell tumors of the skin, was administered iv every 4 days for 11 or 31 treatments to 14 dogs (0.156–5 mg/kg/day) and 11 monkeys (0.5–8 mg/kg/day). Severe doserelated cutaneous toxicity included dermatitis, ulceration at pressure and friction sites, onychoptosis and focal alopecia. Foot pads of dogs housed in wire floor cages were more severely affected than those housed on solid floors. In dogs, lesions occurred only on footpads and the tail tip, while in monkeys the neck, elbows, cubital fossa, ischial callosities and palmar and plantar surfaces of the hands and feet were affected. Microscopic changes at pressure and friction sites included ulceration, focal necrosis, subacute inflammation, hemorrhage, edema and occasional foreign body granulomas. Collagen bundles at both pressure and non-pressure sites showed increased homogeneity, but elastic and reticular fibers showed no evident abnormalities. Atrophy of sweat glands and pilosebaceous apparatus was also observed. Previously reported depression of serum zinc concentrations correlated with the onset of skin lesions, and suggested that zinc deficiency played a role in the pathogenesis of the lesions. Integumentary lesions at pressure and friction sites were a good visual index of bleomycin toxicity.