ACUTE TOXICITY OF MAYTANSINE IN F344 RATS

  • 1 January 1977
    • journal article
    • research article
    • Vol. 61  (7) , 1333-1338
Abstract
The toxicity of the antitumor agent maytansine given by s.c. administration was studied in 5 wk old male F344 rats. The LD50 (14-day) was 0.48 mg/kg. A dose response to drug administration was indicated by body weight changes and diarrhea. A single, acutely toxic dose of maytansine possessed marked activity against dividing cells which was regarded as an important factor in the pathogenesis of acute lesions in tissues with a normal high rate of cell division. Histologically, mitotic figures were observed in many tissues 6-24 h after drug administration. Subsequently, necrotizing lesions led to atrophic changes in gastrointestinal tract mucosa, thymus, spleen, bone marrow and testis. Maytansine also induced hemorrhagic lesions in parenchymatous organs and brain and perivascular mononuclear infiltration in the meninges, and chromatolysis and vacuolation of dorsal root ganglion cells, accompanied by clinical signs of ataxia. Ulcerative skin lesions were observed at the s.c. site of drug administration.