Abstract
Oxidized carboxymethyl-D-manno-n-glucan-DXR conjugates (MG-CM-AD-DXR) prepared via Schiff's base formation possesses not only higher concentration in plasma and tumor but also lower in heart than DXR. In the present investigation, antitumor effects and toxicities of the conjugates were compared with those of DXR. MG-CM [0.5]-AD-DXR (DS of CM groups : 0.5) and MG-CM [1.0] -AD-DXR (DS of CM groups : 1.0)exhibited a growth inhibition similar to DXR against mouse leukemia P388 cells in vitro, but were found to be 2.3-and 1.7-fold more potent than DXR after the intravenous injection in rats bearing Walker 256, respectively. MG-CM[0.5]-AD-DXR conjugate also showed 1.7-fold more effective than DXR in rats bearing Yoshida sar coma. On the other hand, toxicities of MG-CM[0.5]-AD-DXR in rats, reduction of peripheral white blood cells and platelets counts on day 4 and body weight loss, were less than those of DXR after the intravenous injection at a dose of 10 mg/kg as DXR. These toxicities induced by MG-CM[1.0]-AD-DXR were similar to those by DXR, and MG-CM[0.5]-AD-DXR conjugate had less lethal toxicity than DXR in mice.
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