抗肿瘤药物职业暴露对PIVAS工作人员的健康危害评估

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

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(χ^(2)=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。

Objective To evaluate the health hazard of occupational exposure to anti-tumor drugs in the staff of pharma-cy 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 ex-posed 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 consec-utive years(2020 and 2021).The apoptosis rate of peripheral blood cells was measured by flow cytometry.The level of 8-hy-droxy-2'-deoxyguanosine(8-OHdG)was determined by enzyme-linked immunosorbent assay.Results There was no statisti-cal 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 tele-phone in the configuration area was 2286.26,976.82 and 202.42 ng•mL-1 respectively,and the average concentration of CTX was 2991.26,88.12 and 155.40 ng•mL-1,respectively.CTX residues exist in 5-Fu and CTX storage tanks.The re-sults 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(χ^(2)=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 evalu-ating DNA damage and oxidative stress.The level of 8-OHdG in the exposed group was higher than that of the non-ex-posed 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.