Studies on aclacinomycin A resistance in mouse lymphoblastoma

An aclacinomycin A-resistant subline of mouse lymphoblastoma L5178Y cells was isolated by successive treatment of tumor-bearing mice with the antibiotic. IC50 (50% growth inhibition) in culture was observed at a drug concentration of 0.22 micrograms/ml, which was ca. 11 times higher than IC50 for the parental cells. The resistant cell line exhibited cross resistance to mitomycin C, actinomycin D, macromomycin, auromomycin, vinblastine, cytochalasin B, and other anthracyclines: daunorubicin, adriamycin, 4'-O-tetrahydropyranyladriamycin, baumycins A1 and A2, aclacinomycins B and Y, MA144-S1, 1-deoxypyrromycin, cinerubin A, musettamcyin, and pyrromycin. The 1-deoxy group of anthracyclines showed higher degree of cross resistance than the 1-hydroxy group. No significant cross resistance was found with bleomycin A2, neothramycin and blasticidin S. The resistance to aclacinomycin A and cross resistance to adriamycin were also demonstrated by the method of uridine incorporation. The accumulation or retention studies with [3H]adriamycin revealed that the resistance may be due to decreased uptake and increased efflux of the antibiotic in the resistant cells.