Mascioli D W, Estensen R D
Cancer Res. 1984 Aug;44(8):3280-5.
The cells of the human promyelocytic leukemia cell line (HL60) stop growing and differentiate into macrophage-like cells when exposed to nM concentrations of the phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). By exposing cells to the frameshift mutagen ICR-191 and subsequently selecting for resistance to the differentiating effects of nM amounts of TPA, we have isolated TPA-insensitive variants. These variants can grow in up to 320 nM TPA concentrations and do not differentiate into morphologically or functionally mature macrophages. The number of phorbol ester receptors, their affinity for phorbol dibutyrate, and the regulation of receptors are the same as for wild-type HL60 cells. As the resistance to TPA increases in the variants, so does the number of cells with increased ploidy. Wild-type HL60 cells are nearly 100% hypodiploid with a modal chromosome number of 43, while a partially TPA-resistant variant (DM30) has 30% hyperdiploid cells with a mean chromosomal number of 70, and a completely resistant variant (DM90) is 93% hyperdiploid averaging 74 chromosomes/cell. The variants differentiate into neutrophils in response to dimethyl sulfoxide but are defective in respiratory burst activity as assayed by the reduction of the dye nitroblue tetrazolium. These variants could be useful in determining the mode of action of TPA in the promotion of tumors.
人早幼粒细胞白血病细胞系（HL60）的细胞在暴露于纳摩尔浓度的佛波酯肿瘤启动子12 - O - 十四酰佛波醇 - 13 - 乙酸酯（TPA）时会停止生长并分化为巨噬细胞样细胞。通过将细胞暴露于移码诱变剂ICR - 191，随后选择对纳摩尔量TPA的分化作用具有抗性的细胞，我们分离出了对TPA不敏感的变体。这些变体可以在高达320 nM的TPA浓度下生长，并且不会分化为形态或功能成熟的巨噬细胞。佛波酯受体的数量、它们对佛波二丁酸酯的亲和力以及受体的调节与野生型HL60细胞相同。随着变体对TPA的抗性增加，多倍体增加的细胞数量也增加。野生型HL60细胞几乎100%为亚二倍体，众数染色体数为43，而部分对TPA有抗性的变体（DM30）有30%的超二倍体细胞，平均染色体数为70，完全抗性的变体（DM90）93%为超二倍体，平均每个细胞有74条染色体。这些变体在二甲基亚砜的作用下分化为中性粒细胞，但在用染料硝基蓝四氮唑还原法测定的呼吸爆发活性方面存在缺陷。这些变体可用于确定TPA在肿瘤促进中的作用方式。
