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.
National Institute of Oncology, Budapest, Hungary.
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Institóris
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Szikla
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Otvös
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Gál
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