Toxicity of 3'-deamino-3'-(3-cyano-4-morpholinyl) doxorubicin and doxorubicin in nude mice bearing human tumour xenografts.
The toxicity of the intensely potent anthracycline 3'deamino-3'-(3-cyano-4-morpholinyl)doxorubicin (MRA-CN) has been evaluated in nude mice bearing human colonic cancer xenografts. In addition to dose related toxicity manifested as weight loss and effects on the haematology profile, we obtained evidence of cardiotoxicity with MRA-CN, which has not been reported previously. Even a single dose of 0.012 mg kg-1 could induce significant myocardial changes as seen by electron microscopy. Our results suggest that nude mice bearing human tumour xenografts may offer a very sensitive model for the evaluation of anthracycline induced cardiomyopathy. In view of the potential of MRA-CN in cancer treatment, these results need to be confirmed and extended.
Ford
C H
CH
Oncology Research, Department of Surgery, Faculty of Medicine, Memorial University, St. John's, Newfoundland, Canada.
Richardson
V J
VJ
Pushpanathan
C
C
Ali
S K
SK
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000633:toxicity; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009206:Myocardium / Q000473:pathology; D009368:Neoplasm Transplantation
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; C038555:3'-deamino-3'-(3-cyano-4-morpholinyl)doxorubicin