Characterization of resistance to VP-16 in human leukemic cell line.

SAIJO, Y., KUMANO, N., TOKUE, Y., SATOH, K., OIZUMI, K. and MOTOMIYA, M. Characterization of Resistance to VP-16 in Human Leukemic Cell Line. Tohoku J. Exp. Med., 1989, 159 (4), 299-306-Resistance mechanism was studied in the VP-16-resistant human leukemic cell line (THP-1/E) which was developed by continuous drug exposure. The drug uptake and efflux studies revealed no decrease in net cellular drug accumulation. VP-16-induced DNA single- and double-strand breaks in the whole THP-1/E cells decreased significantly compared to the sensitive counterpart as assessed by alkaline elution methods. Decrease in DNA SSBs was also observable in the isolated nuclei from the THP-1/E cells. The resistance to VP-16 in THP-1/E appeared to be independent of altered membrane permeability, and more likely to be associated with decreased VP-16-mediated DNA cleavage.