Absence of cross-resistance between two alkylating agents: BCNU vs bifunctional galactitol.
Dianhydrogalactitol (DAG) increased the life span of both BCNU-sensitive and -resistant L1210 tumor-bearing mice. However, the BCNU-resistant strain showed slightly lower sensitivity against DAG, which could be overcome by an increase in drug dose of ca. 20%. The somewhat lower sensitivity was proportional to a slightly reduced DNA cross-linking formation induced by DAG in BCNU-resistant cells. The amount of DNA cross-links was determined by measurement of the 1,6-di(guaninyl)-galactitol content of DNA. The slight reduction in cross-links is not attributable to DNA repair but rather to other factors that seem to prevent the formation of DNA-drug adducts. The absence of cross-resistance is explained by different kinds of DNA damage caused by the two alkylating agents and the presumably different defense mechanisms developed by cells against these lesions.
Institóris
E
E
National Institute of Oncology, Budapest, Hungary.
Szikla
K
K
Otvös
L
L
Gál
F
F
D000477:Alkylating Agents / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D002330:Carmustine / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D003432:Cross-Linking Reagents / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D004273:DNA, Neoplasm / Q000187:drug effects; D003961:Dianhydrogalactitol / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D007939:Leukemia L1210 / Q000188:drug therapy / Q000401:mortality; D051379:Mice; D013402:Sugar Alcohols / Q000627:therapeutic use*
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D004273:DNA, Neoplasm; D013402:Sugar Alcohols; D003961:Dianhydrogalactitol; C027991:dianhydro-3,4-diacetylgalactitol; D002330:Carmustine