Abstract
With increasing numbers of cancer cases, the use of antineoplastic agents is expected to rise. This will be accompanied by an increase in occupational exposure, which can cause unwanted health effects in workers. Our aim was to give an overview of genotoxic and epigenetic effects after occupational exposure to antineoplastic agents and to assess the concentration−effect relation. Four databases were searched for papers investigating genotoxic and/or epigenetic effects of occupational exposure to antineoplastic agents. Out of the 245 retrieved papers, 62 were included in this review. In this systematic literature review, we confirmed that exposure of healthcare workers to antineoplastic agents can lead to genotoxic damage. However, we observed a lack of data on exposure as well as genotoxic and epigenetic effects in workers other than healthcare workers. Furthermore, gaps in the current knowledge regarding the potential epigenetic effects caused by antineoplastic drug exposure and regarding the link between internal antineoplastic drug concentration and genotoxic and epigenetic effects after occupational exposure to antineoplastic agents were identified, offering a first step for future research.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
Data supporting the findings formulated in this paper are available within the article or the supplementary material.
References
Araújo R, Ramalhete L, Paz H et al (2021) A new method to predict genotoxic effects based on serum molecular profile. Spectrochim Acta A Mol Biomol Spectrosc 255:119680. https://doi.org/10.1016/j.saa.2021.119680
Aristizabal-Pachon AF, Castillo WO (2020) Genotoxic evaluation of occupational exposure to antineoplastic drugs. Toxicol Res 36:29–36. https://doi.org/10.1007/s43188-019-00003-7
Berdasco M, Esteller M (2010) Aberrant epigenetic landscape in cancer: how cellular identity goes awry. Dev Cell 19:698–711. https://doi.org/10.1016/j.devcel.2010.10.005
Bouraoui S, Brahem A, Tabka F et al (2011) Assessment of chromosomal aberrations, micronuclei and proliferation rate index in peripheral lymphocytes from Tunisian nurses handling cytotoxic drugs. Environ Toxicol Pharmacol 31:250–257. https://doi.org/10.1016/j.etap.2010.11.004
Brumen V, Horvat D (1996) Work environment influence on cytostatics-induced genotoxicity in oncologic nurses. Am J Ind Med 30:67–71. https://doi.org/10.1002/(SICI)1097-0274(199607)30:1%3c67::AID-AJIM11%3e3.0.CO;2-6
Burgaz S, Karahalıl B, Bayrak P et al (1999) Urinary cyclophosphamide excretion and micronuclei frequencies in peripheral lymphocytes and in exfoliated buccal epithelial cells of nurses handling antineoplastics. Mutat Res Genetic Toxicol Environ Mutagen 439:97–104. https://doi.org/10.1016/S1383-5718(98)00180-6
Burgaz S, Karahalil B, Canli Z et al (2002) Assessment of genotoxic damage in nurses occupationally exposed to antineoplastics by the analysis of chromosomal aberrations. Hum Exp Toxicol 21:129–135. https://doi.org/10.1191/0960327102ht230oa
Cavallo D, Ursini CL, Perniconi B et al (2005) Evaluation of genotoxic effects induced by exposure to antineoplastic drugs in lymphocytes and exfoliated buccal cells of oncology nurses and pharmacy employees. Mutat Res Genetic Toxicol Environ Mutagen 587:45–51. https://doi.org/10.1016/j.mrgentox.2005.07.008
Cavallo D, Ursini CL, Omodeo-Salè E, Iavicoli S (2007) Micronucleus induction and FISH analysis in buccal cells and lymphocytes of nurses administering antineoplastic drugs. Mutat Res Genetic Toxicol Environ Mutagen 628:11–18. https://doi.org/10.1016/j.mrgentox.2006.10.014
Cavallo D, Ursini CL, Rondinone B, Iavicoli S (2009) Evaluation of a suitable DNA damage biomarker for human biomonitoring of exposed workers. Environ Mol Mutagen 50:781–790. https://doi.org/10.1002/em.20501
Choudhuri S, Kaur T, Jain S et al (2021) A review on genotoxicity in connection to infertility and cancer. Chem Biol Interact 345:109531. https://doi.org/10.1016/j.cbi.2021.109531
Connor T, McLauchlan R, Vandenbroucke J (2007) Preface. J Oncol Pharm Pract 13:1–2. https://doi.org/10.1177/1078155207082350
Connor TH, DeBord DG, Pretty JR et al (2010) Evaluation of antineoplastic drug exposure of health care workers at three university-based US Cancer centers. J Occup Environ Med 52:1019–1027. https://doi.org/10.1097/JOM.0b013e3181f72b63
Cornetta T, Padua L, Testa A et al (2008) Molecular biomonitoring of a population of nurses handling antineoplastic drugs. Mutat Res Genetic Toxicol Environ Mutagen 638:75–82. https://doi.org/10.1016/j.mrfmmm.2007.08.017
Crul M, Hilhorst S, Breukels O et al (2020) Occupational exposure of pharmacy technicians and cleaning staff to cytotoxic drugs in Dutch hospitals. J Occup Environ Hyg 17:343–352. https://doi.org/10.1080/15459624.2020.1776299
De Carvalho DD, Sharma S, You JS et al (2012) DNA methylation screening identifies driver epigenetic events of cancer cell survival. Cancer Cell 21:655–667. https://doi.org/10.1016/j.ccr.2012.03.045
de Jonge ME, Huitema ADR, Rodenhuis S, Beijnen JH (2005) Clinical pharmacokinetics of cyclophosphamide. Clin Pharmacokinet 44:1135–1164. https://doi.org/10.2165/00003088-200544110-00003
El-Ebiary AA, Abuelfadl AA, Sarhan NI (2013) Evaluation of genotoxicity induced by exposure to antineoplastic drugs in lymphocytes of oncology nurses and pharmacists. J Appl Toxicol 33:196–201. https://doi.org/10.1002/jat.1735
Fakher HM, Metwally ES, El-Shafey RSH (2020) The potential genotoxic effects of antineoplastic drugs in occupationally exposed nurses. Asia Pac J Med Toxicol 9(2):60–66. https://doi.org/10.22038/apjmt.2020.16388
Farmer PB, Sepai O, Lawrence R et al (1996) Biomonitoring human exposure to environmental carcinogenic chemicals. Mutagenesis 11:363–381. https://doi.org/10.1093/mutage/11.4.363
Friedman B, Cronstein B (2019) Methotrexate mechanism in treatment of rheumatoid arthritis. Jt Bone Spine 86:301–307. https://doi.org/10.1016/j.jbspin.2018.07.004
Fuchs J, Hengstler JG, Jung D et al (1995) DNA damage in nurses handling antineoplastic agents. Mutat Res Genet Toxicol 342:17–23. https://doi.org/10.1016/0165-1218(95)90086-1
Fucic A, Jazbec A, Mijic A et al (1998) Cytogenetic consequences after occupational exposure to antineoplastic drugs. Mutat Res Genetic Toxicol Environ Mutagen 416:59–66. https://doi.org/10.1016/S1383-5718(98)00084-9
Graeve CU, McGovern PM, Alexander B et al (2017) Occupational exposure to antineoplastic agents. Workplace Health Saf 65:9–20. https://doi.org/10.1177/2165079916662660
Gulten T, Evke E, Ercan I et al (2011) Lack of genotoxicity in medical oncology nurses handling antineoplastic drugs: Effect of work environment and protective equipment. Work 39:485–489. https://doi.org/10.3233/WOR-2011-1198
Hall AL, Davies HW, Demers PA et al (2013) Occupational exposures to antineoplastic drugs and ionizing radiation in Canadian veterinary settings: findings from a National Surveillance Project. Can J Public Health 104:e460–e465. https://doi.org/10.17269/cjph.104.4167
Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674. https://doi.org/10.1016/j.cell.2011.02.013
Hedmer M, Wohlfart G (2012) Hygienic guidance values for wipe sampling of antineoplastic drugs in Swedish hospitals. J Environ Monit 14:1968. https://doi.org/10.1039/c2em10704j
Hessel H, Radon K, Pethran A et al (2001) The genotoxic risk of hospital, pharmacy and medical personnel occupationally exposed to cytostatic drugs—evaluation by the micronucleus assay. Mutat Res Genetic Toxicol Environ Mutagen 497:101–109. https://doi.org/10.1016/S1383-5718(01)00236-4
Hongping D, Zhang M, He J et al (2005) Investigating genetic damage in workers occupationally exposed to methotrexate using three genetic end-points. Mutagenesis 20:351–357. https://doi.org/10.1093/mutage/gei048
Hongping D, Jianlin L, Meibian Z et al (2006) Detecting the cytogenetic effects in workers occupationally exposed to vincristine with four genetic tests. Mutat Res Genetic Toxicol Environ Mutagen 599:152–159. https://doi.org/10.1016/j.mrfmmm.2006.02.003
Huang YW, Jian L, Zhang MB et al (2012) An investigation of oxidative dna damage in pharmacy technicians exposed to antineoplastic drugs in two Chinese hospitals using the urinary 8-OHdG assay. Biomed Environ Sci 25:109–116. https://doi.org/10.3967/0895-3988.2012.01.016
Huang X, Gao C, Cai W et al (2022) Effect of occupational exposure to antineoplastic drugs on DNA damage in nurses: a cross-sectional study. Occup Environ Med 79:253–258. https://doi.org/10.1136/oemed-2021-107913
IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, International Agency for Research on Cancer (1987) Overall evaluations of carcinogenicity: an updating of IARC monographs, volumes 1 to 42. International Agency for Research on Cancer
IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, International Agency for Research on Cancer (1990) Pharmaceutical drugs. IARC
IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, International Agency for Research on Cancer (2000) Some antiviral and antineoplastic drugs, and other pharmaceutical agents. IARC
IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, International Agency for Research on Cancer (2012) Monographs on the evaluation of carcinogenic risks to humans
Izdes S, Sardas S, Kadioglu E et al (2009) Assessment of genotoxic damage in nurses occupationally exposed to anaesthetic gases or antineoplastic drugs by the comet assay. J Occup Health 51:283–286. https://doi.org/10.1539/joh.M8012
Jakab MG, Major J, Tompa A (2001) Follow-up genotoxicological monitoring of nurses handling antineoplastic drugs. J Toxicol Environ Health A 62:307–318. https://doi.org/10.1080/152873901300018011
Jiang H, Panda S, Gekara NO (2019) Comet and micronucleus assays for analyzing DNA damage and genome integrity. Methods Enzymol 625:299–307. https://doi.org/10.1016/bs.mie.2019.05.015
Kašuba V, Rozgaj R, Garaj-Vrhovac V (1999) Analysis of sister chromatid exchange and micronuclei in peripheral blood lymphocytes of nurses handling cytostatic drugs. J Appl Toxicol 19:401–404. https://doi.org/10.1002/(SICI)1099-1263(199911/12)19:6%3c401::AID-JAT592%3e3.0.CO;2-H
Kevekordes S, Gebel TW, Hellwig M et al (1998) Human effect monitoring in cases of occupational exposure to antineoplastic drugs: a method comparison. Occup Environ Med 55:145–149. https://doi.org/10.1136/oem.55.3.145
Kim J, Chan JJ (2017) Cyclophosphamide in dermatology. Australas J Dermatol 58:5–17. https://doi.org/10.1111/ajd.12406
Koller M, Böhlandt A, Haberl C et al (2018) Environmental and biological monitoring on an oncology ward during a complete working week. Toxicol Lett 298:158–163. https://doi.org/10.1016/j.toxlet.2018.05.002
Kopjar N (2001) Application of the alkaline comet assay in human biomonitoring for genotoxicity: a study on Croatian medical personnel handling antineoplastic drugs. Mutagenesis 16:71–78. https://doi.org/10.1093/mutage/16.1.71
Kopjar N, Garaj-Vrhovac V, Kašuba V et al (2009a) Assessment of genotoxic risks in Croatian health care workers occupationally exposed to cytotoxic drugs: a multi-biomarker approach. Int J Hyg Environ Health 212:414–431. https://doi.org/10.1016/j.ijheh.2008.10.001
Kopjar N, Kašuba V, Rozgaj R et al (2009b) The genotoxic risk in health care workers occupationally exposed to cytotoxic drugs—a comprehensive evaluation by the SCE assay. J Environ Sci Health Part A 44:462–479. https://doi.org/10.1080/10934520902719845
Ladeira C, Viegas S, Pádua M et al (2014) Assessment of genotoxic effects in nurses handling cytostatic drugs. J Toxicol Environ Health A 77:879–887. https://doi.org/10.1080/15287394.2014.910158
Laffon B, Teixeira JP, Silva S et al (2005) Genotoxic effects in a population of nurses handling antineoplastic drugs, and relationship with genetic polymorphisms in DNA repair enzymes. Am J Ind Med 48:128–136. https://doi.org/10.1002/ajim.20189
Liao H, Bi L, Wei J, Song X (2017) Evaluation of apoptosis induced by exposure to antineoplastic drugs in peripheral blood lymphocytes of nurses. Mol Med Rep 16:8103–8109. https://doi.org/10.3892/mmr.2017.7589
Lu Y, Liu Y, Yang C (2017) Evaluating in vitro DNA damage using comet assay. J vis Exp. https://doi.org/10.3791/56450
Mader RM, Kokalj A, Kratochvil E et al (2009) Longitudinal biomonitoring of nurses handling antineoplastic drugs. J Clin Nurs 18:263–269. https://doi.org/10.1111/j.1365-2702.2007.02189.x
Mahmoodi M, Soleyman-Jahi S, Zendehdel K et al (2017) Chromosomal aberrations, sister chromatid exchanges, and micronuclei in lymphocytes of oncology department personnel handling anti-neoplastic drugs. Drug Chem Toxicol 40:235–240. https://doi.org/10.1080/01480545.2016.1209678
Major J, Jakab MG, Tompa A (1999) The frequency of induced premature centromere division in human populations occupationally exposed to genotoxic chemicals. Mutat Res Genetic Toxicol Environ Mutagen 445:241–249. https://doi.org/10.1016/S1383-5718(99)00129-1
Maluf SW, Erdtmann B (2000) Follow-up study of the genetic damage in lymphocytes of pharmacists and nurses handling antineoplastic drugs evaluated by cytokinesis-block micronuclei analysis and single cell gel electrophoresis assay. Mutat Res Genetic Toxicol Environ Mutagen 471:21–27. https://doi.org/10.1016/S1383-5718(00)00107-8
McDiarmid MA, Kolodner K, Humphrey F et al (1992) Baseline and phosphoramide mustard-induced sister-chromatid exchanges in pharmacists handling anti-cancer drugs. Mutat Res Genet Toxicol 279:199–204. https://doi.org/10.1016/0165-1218(92)90067-A
McDiarmid MA, Oliver MS, Roth TS et al (2010) Chromosome 5 and 7 abnormalities in oncology personnel handling anticancer drugs. J Occup Environ Med 52:1028–1034. https://doi.org/10.1097/JOM.0b013e3181f73ae6
McDiarmid MA, Rogers B, Oliver MS (2014) Chromosomal effects of non-alkylating drug exposure in oncology personnel. Environ Mol Mutagen 55:369–374. https://doi.org/10.1002/em.21852
Milković-Kraus S, Kraus O, Kršnjavi H, Kubelka D (1992) Environmental effects on chromosomes in oncology and radiology department personnel. Prev Med (baltim) 21:498–502. https://doi.org/10.1016/0091-7435(92)90056-N
Moretti M, Grollino MG, Pavanello S et al (2015) Micronuclei and chromosome aberrations in subjects occupationally exposed to antineoplastic drugs: a multicentric approach. Int Arch Occup Environ Health 88:683–695. https://doi.org/10.1007/s00420-014-0993-y
Mrđanović J, Jungić S, Šolajić S et al (2012) Effects of orally administered antioxidants on micronuclei and sister chromatid exchange frequency in workers professionally exposed to antineoplastic agents. Food Chem Toxicol 50:2937–2944. https://doi.org/10.1016/j.fct.2012.04.027
Mrđanović J, Šolajić S, Srđenović-Čonić B et al (2021) The oxidative stress parameters as useful tools in evaluating the DNA damage and changes in the complete blood count in hospital workers exposed to low doses of antineoplastic drugs and ionizing radiation. Int J Environ Res Public Health 18:8445. https://doi.org/10.3390/ijerph18168445
Mucci N, Dugheri S, Farioli A et al (2020) Occupational exposure to antineoplastic drugs in hospital environments: potential risk associated with contact with cyclophosphamide- and ifosfamide-contaminated surfaces. Med Pr 71:519–529. https://doi.org/10.13075/mp.5893.00931
Mušák Ľ, Halašová E, Matáková T et al (2009) Comparison of chromosomal aberrations frequency and polymorphism of GSTs genes in workers occupationally exposed to cytostatics or anaesthetics. Interdiscipl Toxicol. https://doi.org/10.2478/v10102-009-0016-0
Mušák L, Smerhovsky Z, Halasova E et al (2013) Chromosomal damage among medical staff occupationally exposed to volatile anesthetics, antineoplastic drugs, and formaldehyde. Scand J Work Environ Health 39:618–630. https://doi.org/10.5271/sjweh.3358
National Institute for Occupational Safety and Health (2004a) Preventing occupational exposures to antineoplastic and other hazardous drugs in health care settings
National Institute for Occupational Safety and Health (2004b) Antineoplastic agents—occupational hazards in hospitals
Ness SLR, Mascarenhas MÁ, Arbo MD et al (2021) Occupational exposure assessment in professionals who manipulate and administer antineoplastic drugs in a university hospital in Southern Brazil. J Oncol Pharm Pract 27:1205–1213. https://doi.org/10.1177/10781552211003638
Norppa H, Sorsa M, Vainio H et al (1980) Increased sister chromatid exchange frequencies in lymphocytes of nurses handling cytostatic drugs. Scand J Work Environ Health 6:299–301. https://doi.org/10.5271/sjweh.2605
Oltulu Ç, Yesil Devecioglu T, Akinci M et al (2019) Evaluation of genotoxicity risk in health care workers exposed to antineoplastic drugs. Clin Exp Health Sci. https://doi.org/10.33808/clinexphealthsci.563988
Page MJ, McKenzie JE, Bossuyt PM et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. https://doi.org/10.1136/bmj.n71
Pilger A, Köhler I, Stettner H et al (2000) Long-term monitoring of sister chromatid exchanges and micronucleus frequencies in pharmacy personnel occupationally exposed to cytostatic drugs. Int Arch Occup Environ Health 73:442–448. https://doi.org/10.1007/s004200000164
Power LA, Coyne JW (2018) ASHP guidelines on handling hazardous drugs. Am J Health Syst Pharm 75:1996–2031. https://doi.org/10.2146/ajhp180564
Rekhadevi PV, Sailaja N, Chandrasekhar M et al (2007) Genotoxicity assessment in oncology nurses handling anti-neoplastic drugs. Mutagenesis 22:395–401. https://doi.org/10.1093/mutage/gem032
Rodríguez-Montero HM, Argote-Pelegrino E, Díaz-Curbelo A, Cuétara-Lugo EB (2016) Genotoxicity biomarkers for monitoring occupational exposure to antineoplastic drugs. Pharmacogn Res 4:122–133
Rombaldi F, Cassini C, Salvador M et al (2008) Occupational risk assessment of genotoxicity and oxidative stress in workers handling anti-neoplastic drugs during a working week. Mutagenesis 24:143–148. https://doi.org/10.1093/mutage/gen060
Roussel C, Witt KL, Shaw PB, Connor TH (2019) Meta-analysis of chromosomal aberrations as a biomarker of exposure in healthcare workers occupationally exposed to antineoplastic drugs. Mutat Res Genetic Toxicol Environ Mutagen 781:207–217. https://doi.org/10.1016/j.mrrev.2017.08.002
Rubeš J, Kucharová S, Vozdová M et al (1998) Cytogenetic analysis of peripheral lymphocytes in medical personnel by means of FISH. Mutat Res Genetic Toxicol Environ Mutagen 412:293–298. https://doi.org/10.1016/S1383-5718(97)00201-5
Santos AN, Oliveira RJ, Pessatto LR et al (2020) Biomonitoring of pharmacists and nurses at occupational risk from handling antineoplastic agents†. Int J Pharm Pract 28:506–511. https://doi.org/10.1111/ijpp.12590
Santovito A, Cervella P, Delpero M (2014) Chromosomal damage in peripheral blood lymphocytes from nurses occupationally exposed to chemicals. Hum Exp Toxicol 33:897–903. https://doi.org/10.1177/0960327113512338
Santovito A, Delsoglio M, Manitta E et al (2017) Association of GSTT1 null, XPD 751 CC and 939 CC genotypes with increased levels of genomic damage among hospital pathologists. Biomarkers 22:557–565. https://doi.org/10.1080/1354750X.2017.1322147
Sasaki M, Dakeishi M, Hoshi S et al (2008) Assessment of DNA damage in Japanese nurses handling antineoplastic drugs by the comet assay. J Occup Health 50:7–12. https://doi.org/10.1539/joh.50.7
Selevan SG, Lindbohm M-L, Hornung RW, Hemminki K (1985) A study of occupational exposure to antineoplastic drugs and fetal loss in nurses. N Engl J Med 313:1173–1178. https://doi.org/10.1056/NEJM198511073131901
Smith AN, Klahn S, Phillips B et al (2018) ACVIM small animal consensus statement on safe use of cytotoxic chemotherapeutics in veterinary practice. J Vet Intern Med 32:904–913. https://doi.org/10.1111/jvim.15077
Sorsa M, Pyy L, Salomaa S et al (1988) Biological and environmental monitoring of occupational exposure to cyclophosphamide in industry and hospitals. Mutat Res Genet Toxicol 204:465–479. https://doi.org/10.1016/0165-1218(88)90042-0
Szendi K, Hornyák L, Varga C (2017) Multi-endpoint biological monitoring in combined, carcinogenic occupational exposures. Int J Environ Health Res 27:323–331. https://doi.org/10.1080/09603123.2017.1339783
Tompa A, Jakab MG, Major J et al (2000) The somatostatin analogue peptide TT-232 induces apoptosis and chromosome breakage in cultured human lymphocytes. Mutat Res Genetic Toxicol Environ Mutagen 465:61–68. https://doi.org/10.1016/S1383-5718(99)00212-0
Tompa A, Jakab M, Biro A et al (2006) Chemical safety and health conditions among hungarian hospital nurses. Ann NY Acad Sci 1076:635–648. https://doi.org/10.1196/annals.1371.054
Ündeğer Ü, Başaran N, Kars A, Güç D (1999) Assessment of DNA damage in nurses handling antineoplastic drugs by the alkaline COMET assay. Mutat Res Genetic Toxicol Environ Mutagen 439:277–285. https://doi.org/10.1016/S1383-5718(99)00002-9
Ursini CL, Cavallo D, Colombi A et al (2006) Evaluation of early DNA damage in healthcare workers handling antineoplastic drugs. Int Arch Occup Environ Health 80:134–140. https://doi.org/10.1007/s00420-006-0111-x
Ursini CL, Omodeo Salè E, Fresegna AM et al (2019) Antineoplastic drug occupational exposure: a new integrated approach to evaluate exposure and early genotoxic and cytotoxic effects by no-invasive Buccal Micronucleus Cytome Assay biomarker. Toxicol Lett 316:20–26. https://doi.org/10.1016/j.toxlet.2019.08.022
Valanis B, Vollmer WM, Steele P (1999) Occupational exposure to antineoplastic agents: self-reported miscarriages and stillbirths among nurses and pharmacists. J Occup Environ Med 41:632–638. https://doi.org/10.1097/00043764-199908000-00004
Verscheure E, Creta M, Vanoirbeek J et al (2020) Environmental contamination and occupational exposure of Algerian hospital workers. Front Public Health. https://doi.org/10.3389/fpubh.2020.00374
Villarini M, Dominici L, Piccinini R et al (2011) Assessment of primary, oxidative and excision repaired DNA damage in hospital personnel handling antineoplastic drugs. Mutagenesis 26:359–369. https://doi.org/10.1093/mutage/geq102
Villarini M, Dominici L, Fatigoni C et al (2012) Biological effect monitoring in peripheral blood lymphocytes from subjects occupationally exposed to antineoplastic drugs: assessment of micronuclei frequency. J Occup Health 54:405–415. https://doi.org/10.1539/joh.12-0038-OA
Villarini M, Gianfredi V, Levorato S et al (2016) Occupational exposure to cytostatic/antineoplastic drugs and cytogenetic damage measured using the lymphocyte cytokinesis-block micronucleus assay: a systematic review of the literature and meta-analysis. Mutat Res Rev Mutat Res 770:35–45. https://doi.org/10.1016/j.mrrev.2016.05.001
Yoshida J, Kosaka H, Tomioka K, Kumagai S (2006) Genotoxic risks to nurses from contamination of the work environment with antineoplastic drugs in Japan. J Occup Health 48:517–522. https://doi.org/10.1539/joh.48.517
Zare Sakhvidi MJ, Hajaghazadeh M, Mostaghaci M et al (2016) Applicability of the comet assay in evaluation of DNA damage in healthcare providers’ working with antineoplastic drugs: a systematic review and meta-analysis. Int J Occup Environ Health 22:52–67. https://doi.org/10.1080/10773525.2015.1123380
Zhang J, Bao J, Wang R et al (2016) A multicenter study of biological effects assessment of pharmacy workers occupationally exposed to antineoplastic drugs in Pharmacy Intravenous Admixture Services. J Hazard Mater 315:86–92. https://doi.org/10.1016/j.jhazmat.2016.04.008
Zhang L, Lu Q, Chang C (2020) Epigenetics in health and disease. Adv Exp Med Biol 1253:3–55
Funding
This work was supported by The Research Foundation—Flanders (1SD2322N). The funding sources were not involved in study design or preparation of the article.
Author information
Authors and Affiliations
Contributions
DV: acquisition of data (literature search and study selection), analysis and interpretation of literature, writing—original draft, editing. EV: conceptualisation, writing—draft, writing—review and editing. SAN: acquisition of data (study selection). LG: writing—review and editing, supervision. MG: conceptualisation, writing—review and editing, supervision.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Vanneste, D., Verscheure, E., Srinivasan, A.N. et al. Systematic review of genotoxicity induced by occupational exposure to antineoplastic drugs. Arch Toxicol 97, 1453–1517 (2023). https://doi.org/10.1007/s00204-023-03481-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00204-023-03481-9