Effect of butylated hydroxytoluene on bilineage differentiation of the human HL-60 myeloblastic leukemia cell

Butylated hydroxytoluene (BHT), which has both antioxidant and membrane active properties, has been reported to affect cellular differentiation. We studied its effect on the bipotent lineage differentiation of the important HL-60 human myeloblastic leukemia cell line using reduction of nitroblue tetrazolium, cell cycle analysis, population growth rate, monoclonal antibodies, and morphology. BHT markedly accelerated retinoic acid-induced myelocytic differentiation and dihydroxyvitamin D3-induced monocytic differentiation in a concentration and time-dependent manner. Butylated hydroxyanisole (BHA) had a comparable effect. Preincubation with the compounds was not necessary to evoke the acceleration Other antioxidants and inhibitors of eicosanoid synthesis were inactive. We conclude that the important food preservatives BHT and BHA accelerate the kinetics of terminal differentiation of human leukemia and that this effect is likely due at least in part to their membrane active properties.