Rinaldi M, Tricarico M, Bonmassar E, Parrella P, Barrera G, Fazio V M
Istituto Medicina Sperimentale, CNR, Area di Ricerca Tor Vergata, Rome, Italy.
Anticancer Res. 1998 Sep-Oct;18(5A):3591-5.
4-Hydroxynonenal (HNE) is one of the major breakdown products generated by lipid peroxidation of cellular membranes. The level of lipid peroxidation and the concentration of its products are inversely related to the rate of cell proliferation and directly related to the level of cell differentiation. It has been reported that HNE inhibits DNA synthesis, ornithine decarboxylase (ODC) activity and c-myc expression in different leukemic cells lines. It has also been demonstrated that HNE inhibits proliferation and induces differentiation in HL60 cell line. In the present study the effects of HNE, at concentrations close to those found in the normal tissues, on the NK susceptibility of human K562 target cells were analyzed. Repeated treatments at 45 minutes intervals with 1 microM HNE were performed to maintain the cells in the presence of the aldehyde for 12 hours. The effect of HNE was compared with that obtained in Haemin-treated cells. HNE causes a strong inhibition of cells growth (53% vs. 34% with Haemin) without affecting cell viability. We further investigated the NK susceptibility of K562 cell line upon in vitro treatment with HNE. Cytotoxic activity of mononuclear cells (MNC) from peripheral blood of healthy donors was determined by 4 hours Cr51-release assay. The results obtained, expressed in terms of percentage of specific lysis at different E:T ratios and in terms of KC (10(6)) at the E:T ratio of 50:1, show that HNE treatment of K562 cells leads to a marked reduction of susceptibility to NK cells; this decrease is very close to that found in the K562 cells treated with Haemin used as inducer. Similar results were obtained using MNC pre-treated with beta-interferon (IFN) as effector cells. MNC show a reduced capacity to lyse HNE-treated cells also under the enhancing cytolytic effect of IFN. These results are in line with data obtained with several common inducers of differentiation such as DMSO, retinoic acid or others.
4-羟基壬烯醛（HNE）是细胞膜脂质过氧化产生的主要分解产物之一。脂质过氧化水平及其产物浓度与细胞增殖速率呈负相关，与细胞分化水平呈正相关。据报道，HNE可抑制不同白血病细胞系中的DNA合成、鸟氨酸脱羧酶（ODC）活性和c-myc表达。也已证明，HNE可抑制HL60细胞系的增殖并诱导其分化。在本研究中，分析了浓度接近正常组织中发现的HNE对人K562靶细胞NK敏感性的影响。每隔45分钟用1 microM HNE重复处理，以使细胞在醛存在的情况下维持12小时。将HNE的作用与血红素处理的细胞中获得的作用进行比较。HNE对细胞生长有强烈抑制作用（与血红素处理相比，分别为53%和34%），但不影响细胞活力。我们进一步研究了体外经HNE处理后K562细胞系的NK敏感性。通过4小时的Cr51释放试验测定健康供体外周血单个核细胞（MNC）的细胞毒活性。所获得的结果，以不同E:T比下的特异性裂解百分比以及E:T比为50:1时的KC（10(6)）表示，表明用HNE处理K562细胞会导致对NK细胞的敏感性显著降低；这种降低与用作为诱导剂的血红素处理的K562细胞中发现的降低非常接近。使用经β-干扰素（IFN）预处理的MNC作为效应细胞也获得了类似结果。在IFN增强的溶细胞作用下，MNC对经HNE处理的细胞的裂解能力也降低。这些结果与用几种常见的分化诱导剂（如二甲基亚砜、视黄酸等）获得的数据一致。
