Preclinical toxicological evaluation of fostriecin, a novel anticancer antibiotic, in rats

Fundam Appl Toxicol. 1990 Aug;15(2):258-69. doi: 10.1016/0272-0590(90)90053-m.


Fostriecin, a novel anticancer antibiotic produced by Streptomyces pulveraecus, is believed to act via inhibition of topoisomerase II. Single-dose intravenous administration to rats at dose levels of 8.8 to 48 mg/kg resulted in lethality at dose levels of 35 mg/kg and higher. Major toxic effects were observed primarily at 17.5 mg/kg and higher, were reversible, and consisted of bone marrow hypocellularity, leukopenia, neutropenia, thrombocytopenia, and diffuse necrosis of various lymphoid tissues. The kidney was also identified as a target organ. Renal effects were observed primarily at 20 mg/kg, were reversible, and included increases in serum BUN, creatinine, and 24-hr glucose excretion. Twenty-four-hour excretion of Na+, K+ and urine osmolality were decreased postdosing at 10 and 20 mg/kg. Renal lesions, observed primarily at 20 mg/kg, consisted of vacuolization and necrosis of proximal and distal tubular epithelium at the corticomedullary junction extending into the medulla. Repeated daily intravenous administration of fostriecin for 5 days to rats at dose levels of 2.5 to 26.5 mg/kg resulted in death at 10 mg/kg and above and similar hematologic, bone marrow, lymphoid tissue, and renal changes as observed in the single-dose study. Hematological, bone marrow, lymphoid, and renal changes observed in rats were consistent with the cytotoxic mechanism of action of the compound.

MeSH terms

  • Alkenes / toxicity
  • Animals
  • Antibiotics, Antineoplastic / toxicity*
  • Blood Cell Count
  • Drug Evaluation, Preclinical
  • Female
  • Injections, Intravenous
  • Kidney Diseases / chemically induced
  • Kidney Diseases / pathology
  • Kidney Diseases / physiopathology
  • Male
  • Organ Size / drug effects
  • Polyenes
  • Pyrones
  • Rats
  • Rats, Inbred Strains


  • Alkenes
  • Antibiotics, Antineoplastic
  • Polyenes
  • Pyrones
  • fostriecin