Induction of differentiation in human myeloblastic leukemia ML-1 cells by heptachlor, a chlorinated hydrocarbon...

Effects of heptachlor, an organochlorine pesticide, on human myeloblastic leukemia ML-1 cells were determined. Similar to 12-O-tetradecanoylphorbol-13-acetate (TPA), a known tumor promoter, heptachlor induced cell adherence and formation of extended cytoplasmic pseudopodia in ML-1 cells. The growth of ML-1 was slightly stimulated by low concentrations (less than 30 nM) of heptachlor. A dose-responsive cell death was also observed when ML-1 cells were treated with heptachlor at concentrations greater than 80 microM. Examination by light microscopy of the cells treated with 80 microM heptachlor revealed a gradual appearance of differentiation characteristics in the culture. On Day 3 of the treatment, 41% of the cells remained unchanged as ML-1, 39% of the cells showed changes and apparent cell differentiation, and 20% of the cells were induced to differentiate to monocyte- or macrophage-like cell type. Electron microscopy also revealed cellular differentiation and the presence of monocyte- and macrophage-like cell types (22%) was confirmed by positive esterase staining.