ABOLITION BY CYCLOHEXIMIDE OF CAFFEINE-ENHANCED LETHALITY OF ALKYLATING-AGENTS IN HAMSTER-CELLS

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  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (11) , 4499-4504
Abstract
Greatly enhanced lethality for Syrian hamster cells (baby hamster kidney [BHK] cells and py[polyomavirus-transformed derivative of ]BHK cells) that had been treated with alkylating agents or UV light is proudced by caffeine. Nitrogen mustard [methylbis(.beta.-chloroethyl)amine] (HN2) at 0.5 .mu.M decreased cell viability by only a few percent in the absence of caffeine. The addition of 2 mM caffeine during the first 24 h after HN2 decreased viability more than 95%. Further kinetic studies of the caffeine effects using other alkylating agents indicate the existence of 2 modes by which damaged cells become caffeine sensitive. Treatment with UV light or HN2 makes cells immediately sensitive to caffeine. Cells treated with methyl methanesulfonate or N-methyl-N''-nitro-N-nitrosoguanidine express their maximal caffeine sensitivity only about 15-20 h later. A low concentration of cycloheximide completely abolished this caffeine effect. When 0.36 .mu.M cycloheximide was present, loss of viability was negligible even in the presence of caffeine. Based on further experiments involving the timing of caffeine and cycloheximide additions, caffeine does not affect viability by itself but is involved with some substance such as a protein the rapid synthesis of which is prevented by cycloheximide. This substance does not appear to be needed for recovery from damage, but rather for the action of caffeine in fixing the damage caused by alkylating agents.