Characterization of novel human leukemic cell lines selected for resistance to merbarone, a catalytic inhibitor of DNA topoisomerase II.

Merbarone is a catalytic inhibitor of DNA topoisomerase (topo) II that does not stabilize DNA-topo II cleavable complexes. Although the cytotoxicity of and resistance to complex-stabilizing topo II inhibitors, such as etoposide, is thought to be mediated through stabilization of these complexes, the mechanisms of cytotoxicity and resistance to catalytic inhibitors are not well known. To investigate this issue, we established 12 merbarone-resistant cell lines from human leukemia CEM cells, designated CEM/M70-B1 through -B12.

Subcellular localization of cryptic prolactin receptors in mammary tumor cells.

Primary cultures of carcinogen-induced rat mammary tumors incubated at 37 degrees C with 125I-labeled ovine prolactin (5 ng/ml) accumulate intact prolactin. A steady state is reached at 24--48 h and loss of accumulated prolactin is slow t1/2 24 h). Accumulated prolactin is rapidly released when cryptic prolactin receptors are unmasked by energy depletion, suggesting that accumulated prolactin and cryptic receptors reside in the same cellular compartment.