title: DNA adduct formation by the anticancer drug ellipticine in human leukemia HL-60 and CCRF-CEM cells.
abstract: Ellipticine induces formation of two DNA adducts in leukemia HL-60 and CCRF-CEM cells, identical with deoxyguanosine adducts generated by ellipticine metabolites 13-hydroxyellipticine and 12-hydroxyellipticine in vitro and in vivo. The ellipticine cytotoxicity to HL-60 (IC(50)=0.64microM) and CCRF-CEM cells (IC(50)=4.7microM) correlates with levels of DNA adducts. The different expressions of enzymes activating ellipticine in cells explain this finding. While cytochrome P450 1A1 and cyclooxygenase-1 are expressed in both cells, HL-60 cells express also high levels of another activator, myeloperoxidase. The results suggest the adduct formation as a new mode of antitumor action of ellipticine for leukemia.
authors.affiliation: Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, 128 40 Prague 2, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Poljaková
authors.forename: Eva
authors.initials: E
authors.lastname: Frei
authors.forename: Jacobo E
authors.initials: JE
authors.lastname: Gomez
authors.forename: Dagmar
authors.initials: D
authors.lastname: Aimová
authors.forename: Tomás
authors.initials: T
authors.lastname: Eckschlager
authors.forename: Jan
authors.initials: J
authors.lastname: Hrabeta
authors.forename: Marie
authors.initials: M
authors.lastname: Stiborová
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018736:DNA Adducts / Q000096:biosynthesis*; D004611:Ellipticines / Q000494:pharmacology*; D006801:Humans; D007938:Leukemia / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D018736:DNA Adducts; D004611:Ellipticines; C034192:ellipticine