Isolation, drug sensitivity, and some biochemical and genetical properties of macromomycin-resistant mouse lymphoblastoma L5178Y cells.
A macromomycin (MCR)-resistant subline of mouse lymphoblastoma L5178Y cells was isolated after successive treatment of tumor-bearing mice with the antibiotic for 7 transplant generations, followed by cloning in culture in MCR-containing soft agar medium. The resistant cell line was about 17 times more resistant to MCR than was the parental cell line and exhibited cross-resistance to neocarzinostatin, mitomycin C and adriamycin in a similar degree to MCR. No significant cross-resistance was observed with aclarubicin, bleomycin and neothramycin. Alkaline phosphodiesterase activity in the plasma membrane of resistant cells was higher than that of parental cells. Uptake and efflux studies with [3H]adriamycin suggested that the resistance is due to decreased uptake and increased efflux of the antibiotic in resistant cells. Hybridization studies with MCR-sensitive and -resistant cells showed that the MCR resistance is a codominant trait in somatic cell hybrids.
D000818:Animals; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D004317:Doxorubicin / Q000378:metabolism; D004351:Drug Resistance; D006824:Hybridization, Genetic; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D010455:Peptides / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D010455:Peptides; C001666:auromomycin; D004317:Doxorubicin