抗肿瘤药物职业暴露对PIVAS工作人员的健康危害评估<sup>★</sup>

doi:10.3969/j.issn.2095-1264.2023.06.15

首页 > 过刊浏览>2023年第6期 >759-767. DOI:10.3969/j.issn.2095-1264.2023.06.15

抗肿瘤药物职业暴露对PIVAS工作人员的健康危害评估★
DOI:
                        10.3969/j.issn.2095-1264.2023.06.15
                    
作者:
                        
                        
                    
作者单位:1.昆明医科大学第三附属医院/云南省肿瘤医院，药学部，云南 昆明，650118;2.昆明医科大学第三附属医院/云南省肿瘤医院，肿瘤研究所，云南 昆明，650118;3.昆明医科大学 天然药物药理重点实验室，云南 昆明，650500
作者简介:李琳，女，博士，主管药师，研究方向：天然药物药理学、循证药学。
通讯作者:张红银，男，硕士，副主任药师，研究方向：医院药学、药事管理。
中图分类号:R979.1
基金项目:★云南省基础研究计划——昆明医科大学联合专项［2019FE001（-249）］。

Health hazard assessment of occupational exposure to anti-tumor drugs for PIVAS workers^★

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Affiliation:

1.Department of Pharmacy,;2.Cancer Research Institute, the Third Affiliated Hospital of Kunming Medical University/Yunnan Cancer Hospital, Kunming, 650118, Yunnan, China;3.Key Laboratory of Natural Drug Pharmacology of Kunming Medical University, Kunming, 650500, Yunnan, China

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摘要:

目的采用环境检测与生物检测方法评估静脉药物配置中心（PIVAS）工作人员抗肿瘤药物职业暴露情况。方法于2020年4月随机选取本院PIVAS工作人员50例作为研究对象，根据是否接触过抗肿瘤药物分为暴露组（25例）和非暴露组（25例）。以5-氟尿嘧啶（5-Fu）及环磷酰胺（CTX）为检测标志物，采用超高效液相串联质谱法（UHPLC-MS）连续2年（2020年、2021年）测定PIVAS环境中不同物体擦拭样本及两组研究对象血液、尿液中的5-Fu及CTX浓度；流式细胞术测定外周血细胞凋亡率；酶联免疫吸附法测定8-羟化脱氧鸟苷（8-OHdG）水平。结果工作人员一般情况比较，差异无统计学意义。PIVAS环境中物体表面存在不同程度的5-Fu和CTX污染，配置区振荡器、传递仓内把手及电话表面的5-Fu平均浓度分别为2 286.26、976.82、202.42 ng·mL^-1，CTX平均浓度分别为2 991.26、88.12、155.40 ng·mL^-1；5-Fu及CTX储存箱存在CTX残留。2021年流式结果显示，暴露组单核细胞早期及总凋亡率均显著高于非暴露组（P=0.024， P=0.024）；暴露组中性粒细胞早、晚期凋亡率均高于非暴露组（P=0.004， P<0.001）。两年均在研究对象尿液中检出了CTX残留，暴露组CTX尿液检出率高于非暴露组（χ²=11.52， P<0.001）。暴露组CTX血药浓度高于非暴露组［Z=-7.500， P<0.001 （2020）； Z=-4.500， P<0.001 （2021）］。8-OHdG是公认的评估DNA损伤和氧化应激的敏感生物标志物，暴露组8-OHdG水平明显高于非暴露组（Z=-4.605， P<0.001），提示暴露组DNA损伤程度明显高于非暴露组。结论 PIVAS存在一定程度抗肿瘤药物污染，应重视抗肿瘤药物职业暴露对人体健康的影响并加强防护。

Abstract:

Objective To evaluate the health hazard of occupational exposure to anti-tumor drugs in the staff of pharmacy intravenous admixture services (PIVAS) by using environmental and biological detection methods.Methods In April 2020, 50 staff members were randomly selected from PIVAS of our hospital as the study subjects. They were divided into exposed group (25 cases) and non-exposed group (25 cases) according to whether they had been exposed to anti-tumor drugs or not. Taking 5-fluorouracil (5-Fu) and cyclophosphamide (CTX) as detection markers, the concentrations of 5-Fu and CTX in the blood and urine samples of subjects in two groups, as well as inthe wipe samples of different objects in PIVAS, were determined by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS) for two consecutive years (2020 and 2021). The apoptosis rate of peripheral blood cells was measured by flow cytometry. The level of 8‐hydroxy‐2'‐deoxyguanosine(8-OHdG) was determined by enzyme-linked immunosorbent assay.Results There was no statistical difference in the general situation of the staff. The surface of the objects inPIVAS environment was polluted by 5-Fu and CTX in different degrees. The average concentration of 5-Fu on the surface of oscillator, transfer bin handle and telephone in the configuration area was 2 286.26, 976.82 and 202.42 ng?mL^-1 respectively, and the average concentration of CTX was 2 991.26, 88.12 and 155.40 ng?mL^-1, respectively. CTX residues exist in 5-Fu and CTX storage tanks. The results of flow cytometry in 2021 showed that the early and total apoptosis rates of monocytes both were higherin the exposed group than in the non-exposed group (P=0.024, P=0.024). The early and late apoptosis rates of neutrophils in the exposed group both were higher than in the non-exposed group (P=0.004, P<0.001). CTX residues were detected in urine of the staff in both years, and the detection rate of urinaryCTX of the exposed group was higher than that of the non-exposed group (χ²=11.52, P<0.001). The plasma concentration of CTX in the exposed group was higher than that of the non-exposed group [Z=-7.500, P<0.001 (2020); Z=-4.500, P<0.001 (2021)]. 8-OHdG was recognized as a sensitive biomarker for evaluating DNA damage and oxidative stress. The level of 8-OHdG in the exposed group was higher than that of the non-exposed group (Z=-4.605, P<0.001), indicating that the degree of DNA damage in the exposed group was significantly higher than that in the non-exposed group.Conclusion PIVAS is polluted by anti-tumor drugs to a certain extent, so we should pay attention to the impact of occupational exposure to anti-tumor drugs on human health, and strengthen protection as far as possible.