慢性苯中毒患者脱离苯接触后外周血淋巴细胞微核率与血常规指标变化特征
Variations of peripheral micronucleus frequencies and routine blood test indices in patients with chronic benzene poisoning after leaving benzene-exposed environment
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摘要:
目的 研究慢性苯中毒患者脱离苯接触2~48年后，血常规指标与外周血淋巴细胞微核率变化特征，及二者关系。
方法 以上海市某医院诊断的36例慢性苯中毒患者（确诊后均脱离苯接触）为病例组，按照性别、年龄匹配在社区选择36名健康者作为对照组。对72名研究对象进行血常规检测，并采用胞质分裂阻滞微核实验检测微核率。分别用配对t检验、Poisson回归比较病例组和对照组的血常规结果和微核率，用趋势性检验分析病例组血常规结果与微核率之间的关系，用卡方检验分析微核异常率，用logistic回归模型分析微核率异常的影响因素。
结果 与对照组相比，病例组的白细胞计数下降了1.95×109/L、中性粒细胞下降了0.85×109/L、淋巴细胞下降了0.7×109/L、红细胞计数下降了0.39×1012/L、血红蛋白下降了9.21 g/L及血小板下降了50.17×1012/L，差异均具有统计学意（P < 0.01）；病例组白细胞异常率、中性粒细胞异常率、血红蛋白异常率与对照组差异具有统计学意义（χ2=20.67，P < 0.001；χ2=12.77，P < 0.001；χ2=11.61，P=0.001）；病例组和对照组的外周血淋巴细胞微核率分别为（7.22±2.87）‰和（4.14±1.66）‰，病例组微核率比对照组升高74%（FR=1.74，P < 0.001）。白细胞、中性粒细胞均与微核率呈负相关，Spearman相关系数分别为-0.416、-0.495（P < 0.05，P < 0.01）。病例组18例当前白细胞正常者（≥ 4.0×109/L且≤ 10.0×109/L），其微核率仍高于配对对照组（FR=1.40，P < 0.05）。病例组按脱离苯接触年数分组，与对照组相比，随着脱离年数的增加，三组微核率均升高（FR=1.46，P=0.025；FR=1.92，P < 0.001；FR=1.79，P < 0.001）。三组微核率异常的风险有升高趋势（OR=4.05，P=0.153；OR=27.33，P=0.001；OR=355.26，P=0.001）。
结论 慢性苯中毒患者脱离苯接触后仍会持续存在血液毒性与遗传毒性，微核率比白细胞更加敏感。
Abstract:Objective To analyze the association of blood routine test indices with peripheral micronucleus (MN) frequencies in diagnosed chronic benzene poisoning patients who have been removed from benzene-exposed environment for 2 to 48 years.
Methods Thirty-six patients with chronic benzene poisoning diagnosed in a Shanghai hospital and then leaving benzeneexposed environment were selected as the case group, and another 36 sex-and-age-matched healthy participants elected from a community were grouped as the controls. All participants were subjected to routine blood tests, and cytokinesis-block micronucleus assay was used to detect peripheral MN frequencies. Paired t test and Poisson regression were used to analyze routine blood test results and MN frequencies between the case and control groups. Trend test was applied to analyze the relationship between routine blood test results and MN frequencies of the case group. Chi-square test was used to analyze abnormal MN frequencies. Logistic regression models were used to find out the factors relevant to MN abnormality.
Results Compared with the control group, white blood counts, neutrophil numbers, lymphocyte numbers, red blood counts, hemoglobin, and platelets were significantly decreased by 1.95×109/L, 0.85×109/L, 0.7×109/L, 0.39×1012/L, 9.21 g/L, and 50.17×1012/L in the case group, respectively (P < 0.01). The rates of abnormal white blood counts, abnormal neutrophil numbers, and abnormal hemoglobin in the case group were higher than those in the control group (χ2=20.67, P < 0.001; χ2=12.77, P < 0.001; χ2=11.61, P=0.001, respectively). The MN frequencies in the case group(7.22±2.87)‰ was 74% higher than that in the control group(4.14±1.66)‰ (FR=1.74, P < 0.001). White blood counts and neutrophil numbers were both negatively correlated to MN frequencies, and the Spearman correlation coefficients were -0.416 (P < 0.05) and -0.495 (P < 0.01), respectively. The patients with normal white blood counts (n=18, ≥ 4.0×109/L and ≤ 10.0×109/L) showed higher MN frequencies than those of the paired controls (FR=1.40, P < 0.05). The case group was further separated to three sub-groups according to the years following being removed from benzene exposure. The MN frequencies of the three sub-groups increased with the increasing years following being removed from benzene exposure (FR=1.46, P=0.025; FR=1.92, P < 0.001; FR=1.79, P < 0.001), and the odds ratio of abnormal MN frequencies also increased (OR=4.05, P=0.153; OR=27.33, P=0.001; OR=355.26, P=0.001).
Conclusion Hematotoxicity and genetic toxicity persist in patients with chronic benzene poisoning even after being removed from benzene exposure. MN frequency is more sensitive than white blood counts.
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