Toxicological studies on (2"R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic. Subacute toxicity study in rats.
(2"R)-4'-O-Tetrahydropyranyladriamycin X HCl (THP), a new anthracycline antitumor antibiotic, was administered to Sprague-Dawley rats intraperitoneally for 13 weeks. In rats receiving 0.4 mg/kg/day, piloerection, emaciation, loose feces and thickening of the injection site were evident, and 7 males and 2 females died after week 12. Inferior body weight gain was observed in both sexes starting week 4 approximately 6. The food consumption also decreased. Hematological examination revealed lower counts of total leucocyte and lymphocyte. At termination there were lower spleen, thymus and testes weights, thickening of the walls of the intestine and stomach, gastric ulceration, presence of ascitic fluid, and congestion and thickening at the injection site. Decreases in the lymphocyte populations of the thymus, spleen and lymph nodes were observed microscopically. A decrease in the number of hematopoietic cells in the bone marrow and a degeneration of the germinal epithelium in the testes were also seen, as were gastrointestinal disturbances. These treatment-related effects were mainly confined to rats receiving 0.4 mg/kg/day and to a lesser extent, to rats receiving 0.1 mg/kg/day. The effects on rats receiving 0.025 mg/kg/day were only at the microscopic level. No rats receiving 0.006 mg/kg/day were toxicologically affected.
Tone
H
H
Shirai
M
M
Danks
A P
AP
Lee
P
P
Finn
J P
JP
Ashby
R
R
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity*; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D001854:Bone Marrow Cells; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D006403:Hematologic Tests; D007274:Injections, Intraperitoneal; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; C027260:pirarubicin