Induction of resistance to 6-thioguanine and cytarabine by a range of anticancer drugs in Chinese hamster AA8 cells.
A mutagenicity assay using AA8 Chinese hamster cells has been used to explore the potential of some currently used clinical anticancer drugs to induce cells resistant to 6-thioguanine and cytarabine. Preliminary experiments gave evidence of a "low dose" and "high dose" resistance to cytarabine, and subsequent work considered only the latter of these events. When ethyl methane sulphonate was used as a reference mutagen, induced resistance to cytarabine developed substantially later and at a lower frequency than resistance to 6-thioguanine. Of the clinical drugs tested, carmustine showed the highest ability to induce either 6-thioguanine or cytarabine resistant cells. Bleomycin, daunomycin and amsacrine showed moderate ability, while vincristine was essentially inactive in these assays. Such information could potentially be used in selecting new drug combinations or timing of drug administration in cancer chemotherapy.
Ferguson
L R
LR
Cancer Research Laboratory, University of Auckland Medical School, New Zealand.
Hill
C L
CL
Morecombe
P
P
D000677:Amsacrine / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology; D016466:CHO Cells / Q000187:drug effects* / Q000502:physiology; D002330:Carmustine / Q000494:pharmacology; D002999:Clone Cells; D006224:Cricetinae; D003561:Cytarabine / Q000494:pharmacology*; D004249:DNA Damage; D003630:Daunorubicin / Q000494:pharmacology; D004351:Drug Resistance; D005020:Ethyl Methanesulfonate / Q000494:pharmacology; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects; D013866:Thioguanine / Q000494:pharmacology*; D013997:Time Factors; D059004:Topoisomerase I Inhibitors; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; D000677:Amsacrine; D003561:Cytarabine; D001761:Bleomycin; D005020:Ethyl Methanesulfonate; D013866:Thioguanine; D002330:Carmustine; D003630:Daunorubicin