Antitumor effects of SMANCS on rat mammary tumor induced by 7,12-dimethylbenz[a]anthracene.

We previously found that a high-molecular-weight anticancer agent, polystyrene-co-maleic acid conjugated neocarzinostatin (SMANCS), in which two chains of styrene/maleic acid copolymer are conjugated to the anticancer protein neocarzinostatin (NCS), accumulated more selectively in tumor tissue than in normal tissue and was more stable than NCS in blood. These results indicate that SMANCS should have less systemic toxicity and a better therapeutic effect than NCS. In this study, the antitumor activity and adverse effects of SMANCS were compared with those of NCS by using rat mammary tumor induced by 7,12-dimethylbenz[a]anthracene. When tumors of rats, that had received 7,12-dimethylbenz[a]anthracene (20 mg/kg, one dose, p.o. in oily formulation), became palpable usually after 4-20 weeks, SMANCS treatment was initiated. Thirty days after i.v. administration of SMANCS (0.1 mg/kg 3 times and 0.3 mg/kg 3 times), tumors had shrunk in 35 of 37 rats (a mean weight was about 10% of control value; or decreased to about 30% of the value of before treatment in tumor weight); tumor size had not changed in 1 rat, and in the remaining 1 rat the tumor had enlarged. Thirty days after i.v. administration of NCS, tumors had shrunk in 8 of 14 rats, but the tumor size was unchanged in 1 rat and was enlarged in 5. In the control group, all tumors had enlarged. Development of new tumors was completely prevented by the administration of SMANCS. Histological examination of sequential slices of tumor revealed clear finding of degeneration and tumor encapsulation at 30 days after initial administration of SMANCS, with an accompanying fatty degeneration, but these effects were not observed for tumors treated with NCS. Although red blood cell counts and hemoglobin amounts decreased significantly in rats receiving NCS, no such effects were apparent in the SMANCS group.