Lysis of human promyelocytic HL-60 cells by amphotericin B in combination with 2-chloroethyl-1-nitrosoureas: role of the carbamoylating activity of nitrosoureas.
The combinations of amphotericin B (AmB) with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) or 2-cyclohexyl isocyanate, the carbamoylating decomposition product of CCNU, were more potent in lysing HL-60 cells than the combinations of AmB with 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) or 2-chloroethyl isocyanate, the carbamoylating decomposition product of BCNU. The noncarbamoylating nitrosoureas 1-(2-chlorethyl)-3-(2,6-dioxo-3-piperydyl)-1-nitrosourea and 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose did not alter AmB effects on HL-60 cells. These results indicate that the potentiating action of CCNU and BCNU on the lytic effects of AmB is associated with the carbamoylating activity of these nitrosoureas. It is likely that the greater carbamoylating activity of CCNU, compared to BCNU, is responsible for the differences in potency of the two AmB-drug combinations.
Brajtburg
J
J
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Elberg
S
S
Schechtman
K B
KB
Medoff
G
G
D000666:Amphotericin B / Q000378:metabolism / Q000494:pharmacology*; D002330:Carmustine / Q000494:pharmacology; D002460:Cell Line; D004359:Drug Therapy, Combination; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000378:metabolism; D008130:Lomustine / Q000494:pharmacology; D009607:Nitrosourea Compounds / Q000378:metabolism / Q000494:pharmacology*
D009607:Nitrosourea Compounds; C064107:2-((3-chloroethyl)-3-nitrosoureido)glucopyranose; D008130:Lomustine; D000666:Amphotericin B; C018627:1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidinyl)-1-nitrosourea; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D002330:Carmustine