Effects of benzo[a]pyrene on concanavalin A-stimulated human peripheral blood mononuclear cells in vitro: inhibition of proliferation but no effect on parameters related to the G1 phase of the cell cycle.
Effects of benzo[a]pyrene on concanavalin A-stimulated human peripheral blood mononuclear cells in vitro: inhibition of proliferation but no effect on parameters related to the G1 phase of the cell cycle.
复制标题
苯并[a]芘对刀豆球蛋白 A 刺激的人外周血单核细胞的体外影响：抑制增殖，但对细胞周期 G1 期相关参数没有影响。
DOI：
10.1006/taap.1993.1057
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发表时间：
1993
影响因子：
3.8
通讯作者：
Mudzinski,SP
中科院分区：
文献类型：
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作者：
Mudzinski,SP
环境致癌物苯并[a]芘 (BaP) 的免疫毒性作用已使用小鼠而非人类淋巴细胞进行了评估。由于 BaP 免疫调节的敏感性可能与物种相关，因此在体外研究了 BaP 对多个个体的人外周血单核细胞 (HPBMC) 的影响。在 BaP（10−9 至 10−6M）或载体对照（丙酮）存在下，用 T 细胞丝裂原伴刀豆球蛋白 A (con A) 刺激 HPBMC，并在 3 天后评估 [3H]TdR 掺入、细胞数量、细胞周期分布、活力以及细胞表面或细胞内激活抗原的表达。 IL-2 的产生在 24 小时时进行定量。 [3H]TdR 的掺入是对 BaP 最敏感的参数，相对于对照的 IC50 为 4.5 ± 3.1 × 10−8M，个体范围为 1.8 × 10−8 至 6.6 × l0−8M (n = 15)。 P450 抑制剂 7,8-苯并黄酮 (10−6M) 部分阻止 BaP 对 [3H]TdR 掺入的抑制。要最大程度地抑制此参数，需要 BaP 存在于培养物中 >24 小时。从培养物中回收的细胞数量减少了 l0−8 至 10−6M BaP，但活力仅因 10−7 至 10−6M BaP 略有下降。 BaP 对诱导 IL-2 (CD25) 或转铁蛋白 (CD7 I) 受体的细胞百分比或 24 小时培养上清液中存在的 IL-2 活性量影响很小或没有影响。尽管 BaP 介导的 [3H]TdR 掺入减少，但细胞周期分析表明 10−7 和 10−6M 的 BaP 增加了 S 期细胞的百分比，并相应降低了 G0G1 期细胞的百分比。此外，BaP（10−7 至 10−6M）降低了细胞内激活抗原 PCNA（或 Ki-67）呈阳性的 G0/G1 细胞的百分比，但如果含羞草碱或阿非迪霉素阻止细胞穿过 S 期，则对该百分比没有影响。这些结果表明，BaP 在培养浓度低至 10−8M 时，通过 P450 依赖性过程抑制 con A 刺激的人外周血 T 细胞的 DNA 合成和增殖，但在培养浓度高达 10−6M 时，对测量的 G1 相关事件影响很小或没有影响。
The immunotoxic effects of the environmental carcinogen benzo[a]pyrene (BaP) have been evaluated using mouse, but not human, lymphocytes. Since susceptibility to immunomodulation by BaP may be species-related, the effects of BaP on human peripheral blood mononuclear cells (HPBMC) from several individuals were investigated in vitro. HPBMC were stimulated by the T-cell mitogen concanavalin A (con A) in the presence of BaP (10−9to 10−6M) or vehicle control (acetone) and evaluated after 3 days for [3H]TdR incorporation, cell numbers, cell-cycle distribution, viability, and expression of cell surface or intracellular activation antigens. IL-2 production was quantified at 24 hr. Incorporation of [3H]TdR was the parameter most sensitive to BaP with an IC50relative to controls of 4.5 ± 3.1 × 10−8M with a range for individuals of 1.8 × 10−8to 6.6 × l0−8M (n = 15). The P450 inhibitor 7,8-benzoflavone (10−6M) partially prevented BaP inhibition of [3H]TdR incorporation. Maximum suppression of this parameter required that BaP be present in culture >24 hr. The number of cells recovered from culture was decreased by l0−8to 10−6M BaP, but viability was only slightly diminished by 10−7to 10−6M BaP. BaP had little or no effect on the percentages of cells with induced IL-2 (CD25) or transferrin (CD7 I) receptors or on the amount of IL-2 activity present in 24-hr culture supernatants. Despite the BaP-mediated decrease in [3H]TdR incorporation, cell-cycle analysis indicated that BaP at 10−7and 10−6M increased the percentages of cells in S phase, and correspondingly decreased the percentages of cells in the G0G1, phase. Also, BaP (10−7to 10−6M) decreased the percentages of G0/G1cells that were positive for the intracellular activation antigen PCNA (or Ki-67), but had no affect on this percentage if cells were prevented from traversing S phase by mimosine or aphidicolin. These results suggest that BaP inhibits DNA synthesis and proliferation of con A-stimulated, human peripheral blood T-cells at culture concentrations as low as 10−8M by a P450-dependent process, but has little or no effect on measured G1-associated events at culture concentrations up to 10−6M.