Antitumor effect, cardiotoxicity, and nephrotoxicity of doxorubicin in the IgM solid immunocytoma-bearing LOU/M/WSL rat
Van Hoesel, Q.G.; Steerenberg, P.A.; Vos, J.G.; Hillen, F.C.; Dormans, J.A.
Journal of the National Cancer Institute 72(5): 1141-1150
1984
ISSN/ISBN: 0027-8874 PMID: 6585590 Document Number: 236735
Antitumor activity, cardiotoxicity, and nephrotoxicity induced by doxorubicin were studied in LOU/M/WSL inbred rats each bearing a transplantable solid IgM immunocytoma. Animals with a tumor (diameter, 15.8 +/- 3.3 mm) were treated with iv injections of doxorubicin on 5 consecutive days, followed by 1 weekly injection for 7 weeks (dose range, 0.015-4.0 mg/kg body wt). Tumor regression was observed with 0.5 mg doxorubicin/kg. Complete disappearance of the tumor was induced with 1.0 mg doxorubicin/kg. Histologic evidence of cardiotoxicity scored as grade III was only observed at a dose of 1.0 mg doxorubicin/kg. Light microscopic evidence of renal damage was seen above a dose of 0.5 mg doxorubicin/kg, which resulted in albuminuria and very low serum albumin levels. In the group that received 1.0 mg doxorubicin/kg, the serum albumin level decreased from 33.6 +/- 4.1 to 1.5 +/- 0.5 g/liter. Ascites and hydrothorax were observed simultaneously. The same experiments were performed with non-tumor-bearing rats, in which no major differences were observed. In conclusion, antitumor activity, cardiotoxicity, and nephrotoxicity were studied simultaneously in the same LOU/M/WSL rat. Albuminuria due to renal damage led to extremely low serum albumin levels, so ascites and hydrothorax were not necessarily a consequence of the observed cardiomyopathy.