Resistance mechanisms to topoisomerase poisons: the application of cell culture methods.
A survey is presented of two types of resistance to drugs acting on cellular topoisomerase enzymes, that occurring by altered drug transport and that occurring by altered target interaction. Particular attention is paid to the use of pairs of diagnostic drugs, one susceptible and one refractory to a particular resistance mechanism, in the determination of such resistance in cultured cells. Two pairs of drugs, each including the antitumor agent amsacrine, are used in the analysis of a number of cell lines. Also it is suggested that some normal hemopoietic precursor cells may exhibit two types of multidrug resistance, and that this should be taken into account in determining selectivity of topoisomerase-directed drugs for tumor cells.
Cancer Research Laboratory, University of Auckland School of Medicine, New Zealand.
B C
BC
Baguley
G J
GJ
Finlay
L M
LM
Ching
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000677:Amsacrine / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D001692:Biological Transport; D004249:DNA Damage; D004264:DNA Topoisomerases, Type I / Q000187:drug effects*; D004250:DNA Topoisomerases, Type II / Q000187:drug effects*; D004351:Drug Resistance / Q000235:genetics / Q000502:physiology*; D005784:Gene Amplification; D008562:Membrane Glycoproteins / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D008562:Membrane Glycoproteins; D000677:Amsacrine; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II