Development of resistance to adriamycin (NSC-123127) in Ehrlich ascites tumor in vivo.

Resistance to adriamycin was developed in an originally adriamycin-sensitive wild strain of Ehrlich ascites tumor (EHR 2) in vivo by treatment with the drug during 25 weekly passages of the tumor. The growth of the resistant line was slower than that of the wild tumor. The resistance was stable for more than 25 weeks both when adriamycin treatment was continued and when treatment was discontinued. The adriamycin-resistant tumor showed cross resistance to daunomycin, just as a daunomycin-resistant subline showed cross resistance to adriamycin. In the adriamycin-resistant tumor, cross resistance to vincristine was also found. There was no change in the sensitivity of the tumor to methotrexate, and it remained nearly insensitive to 6-mercaptopurine, while collateral sensitivity to BCNU and cytosine arabinoside was observed. The data obtained are very similar to data obtained with a daunomycin-resistant line of the same tumor. When adriamycin was given intraperitoneally, it was significantly less toxic than daunomycin, while there was no significant difference in growth-inhibiting effect on the wild Ehrlich ascites tumor.