Department of Medical-Surgical Specialties and Public Health University of Perugia, Via del Giochetto, 06122 Perugia, Italy.
Mutagenesis. 2011 May;26(3):359-69. doi: 10.1093/mutage/geq102. Epub 2010 Nov 26.
The International Agency for Research on Cancer has classified several antineoplastic drugs in Group 1 (human carcinogens), among which chlorambucil, cyclophosphamide (CP) and tamoxifen, Group 2A (probable human carcinogens), among which cisplatin, etoposide, N-ethyl- and N-methyl-N-nitrosourea, and Group 2B (possible human carcinogens), among which bleomycins, merphalan and mitomycin C. The widespread use of these mutagenic/carcinogenic drugs in the treatment of cancer has led to anxiety about possible genotoxic hazards to medical personnel handling these drugs. The aim of the present study was to evaluate work environment contamination by antineoplastic drugs in a hospital in Central Italy and to assess the genotoxic risks associated with antineoplastic drug handling. The study group comprised 52 exposed subjects and 52 controls. Environmental contamination was assessed by taking wipe samples from different surfaces in preparation and administration rooms and nonwoven swabs were used as pads for the surrogate evaluation of dermal exposure, 5-fluorouracil and cytarabine were chosen as markers of exposure to antineoplastic drugs in the working environment. The actual exposure to antineoplastic drugs was evaluated by determining the urinary excretion of CP. The extent of primary, oxidative and excision repaired DNA damage was measured in peripheral blood leukocytes with the alkaline comet assay. To evaluate the role, if any, of genetic variants in the extent of genotoxic effects related to antineoplastic drug occupational exposure, the study subjects were genotyped for GSTM1, GSTT1, GSTP1 and TP53 polymorphisms. Primary DNA damage significantly increased in leukocytes of exposed nurses compared to controls. The use of personal protective equipment (i.e. gloves and/mask) was associated with a decrease in the extent of primary DNA damage.
国际癌症研究机构已将几种抗肿瘤药物归类为第 1 组（人类致癌物），其中包括苯丁酸氮芥、环磷酰胺（CP）和他莫昔芬；第 2A 组（可能的人类致癌物），其中包括顺铂、依托泊苷、N-乙基-N-甲基亚硝脲和 N-甲基-N-亚硝脲；第 2B 组（可能的人类致癌物），其中包括博来霉素、美法仑和丝裂霉素 C。这些诱变/致癌药物在癌症治疗中的广泛应用导致了人们对处理这些药物的医务人员可能存在遗传毒性危害的担忧。本研究旨在评估意大利中部一家医院的抗肿瘤药物工作环境污染情况，并评估与抗肿瘤药物处理相关的遗传毒性风险。研究组包括 52 名暴露组和 52 名对照组。通过从准备室和给药室的不同表面采集擦拭样本来评估环境污染，非织造擦拭物用作皮肤暴露替代评估的衬垫，选择 5-氟尿嘧啶和阿糖胞苷作为工作环境中接触抗肿瘤药物的标志物。通过测定 CP 的尿排泄来评估抗肿瘤药物的实际暴露情况。用碱性彗星试验测量外周血白细胞中 DNA 原发性损伤、氧化损伤和切除修复损伤的程度。为了评估遗传变异在与抗肿瘤药物职业暴露相关的遗传毒性效应程度中的作用（如果有），对研究对象进行了 GSTM1、GSTT1、GSTP1 和 TP53 多态性基因分型。与对照组相比，暴露于护士的白细胞中初级 DNA 损伤明显增加。使用个人防护设备（即手套和/或口罩）与初级 DNA 损伤程度降低相关。
