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Published on 1 February 2008

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Hospital workplaces: risks of exposure to carcinogens

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This follow-up study set out to identify cases where prevention measures were not being routinely used, leading to ill-health and
a higher risk of chronic noninfectious disease in the workforce.

Anna Tompa
Professor and Director

Department of Public Health
Semmelweis Medical University
Budapest
Hungary

The scientific community has generally accepted that cancer develops in a multistep fashion, as malignant diseases require a long expression period.1 Molecular pathological studies have established that malignant transformation is determined by thousands of genetic changes in the somatic cells. However, the environment plays a major role in the aetiology of some 70–90% of malignancies, implying that cancers induced by environmental factors can be prevented. The most ­important environmental mutagens are chemical carcinogens.2 In 2006, approximately 10 million chemical ­substances were registered, of which about 75,000 were on the market. Approximately 70 of these were proved to be carcinogenic for humans, while another 300 chemicals were suspected to be carcinogenic based on animal studies. Therefore, the presence of these substances in our local environment must be urgently investigated. Apart from the spontaneous mutations that arise from our way of life, such as smoking, unhealthy eating, alcohol and drug abuse, these additional working environmental exposures can greatly increase our risk of cancer.

Molecular methodology used in cancer prevention and risk assessment
Carcinogens such as chemicals, drugs, physical or biochemical agents can attack DNA, resulting in the creation of cancer genes.1 Genotoxicological monitoring is used in risk assessment of healthcare workers to pick up early chromosomal damages in peripheral blood lymphocytes (PBLs).
Genotoxicity is influenced by different factors, such as exposure level, healthcare workers’ skills, implementation of work safety precautions and personal susceptibility based on genetic vulnerability to cancer. Hazards, therefore, have different values for different fields of activity (eg, radiology, surgery, oncology). One cannot apply and extrapolate data from other countries, especially if they use technology or work safety activities that differ from ours.3,4 Genotoxicology monitoring as a means of risk assessment must always rely on given biological and environmental factors at the place of activity.
The genotoxicology (cytogenetic) monitoring approach has been harmonised with EU directives, in accordance with priorities formulated by the National Welfare Bulletin and the National Cancer Control Program. Therein, the role of the cytogenetic investigations has been formulated as follows: “By decreasing the risk factors an increasing role is taken by the cytogenetic investigation of those people/workers exposed to higher harmful exposition. They can predict the impact of the mutagens’ action on humans (genotoxicity) and thus the increased possibility of health damage can be foreseen.”5–7
Exposed individuals are always central to our studies. Primary prevention can only be successful if genetic toxicology monitoring can reveal acquired genetic damage, chromosomal aberrations (CAs) and sister chromatide exchanges (SCEs) as soon as possible, when they are still reversible.8,9 Work safety directives must be based upon cytogenetic and other biological and physical parameters, which protect against carcinogens if implemented effectively.9 To provide follow-up in primary prevention, a powerful and already tested genotoxicology (cytogenetic) tool can be used to detect risk factors and ensure the efficacy of primary prevention
measures.10,11

Results
Since 1994, more than 2,000 investigations have been carried out on 717 nurses using the geno‑
toxicology monitor.12,13 These were compared with 94 nonexposed control cases. Nurses from urban and rural hospitals were represented in equal numbers. Their average age ranged from 28 to 45 years. Controls had an average age of 39.9 years, while exposed nurses were generally aged 37.7 years. The number of smokers fluctuated between 26% and 47%, but was much higher among exposed nurses than controls, at 38.2% versus 26.6%, respectively. Regular consumption of alcohol was surprisingly high, at 36.2% in the control group and 68.2% among anaesthetists. The total average was also high at 55.5%.
[[Table2_19]]
Cytogenetic nurse data are compared in Figure 1. It can clearly be seen that many nurses were exposed to sterilising gases in 1993 but this reduced after 1996. Data do not refer to just one work area but are pooled together from hospitals across different regions. We began to study anaesthetists in 2000, but results for those were not favourable as they were exposed to disinfectants, radiation, medicines and isotopes as well as sterilising agents.
[[Table2_19]]As a consequence, 2005 CA values rose above the expected control level of 2.5%. A similar
deteriorating tendency was shown for nurses exposed to cytostatics, where following a temporary
average improvement in 2005 the group average rose to 3.4%.
It is evident that the CA and SCE values were higher for exposed nurses, especially smokers, ­compared with nonexposed nurses.4−6 Although smokers’ CA values did not differ significantly from those of the control group, when exposed tocytostatics they almost doubled. What health changes will this this rise in chromosomal abberrations herald? Does exposure to hospital chemicals increase the risk of certain diseases?
We compared these samples with people who were exposed but did not suffer genotoxicity. From our immune toxicological results it can be concluded that the ratio of T helper (TH), activated T and B cell subpopulations rose significantly compared with the intact group, while natural killer cells and oxidative burst activity markedly declined. The oxidative burst phenomenon therefore correlated not only with iron deficiency (anaemia) but also with the presence of chromosome aberrations.

Conclusion
Statistical data indicate a chronic Hungarian workforce shortage due to overwork, ill-health and increased risk of chronic noninfectious diseases. Oncology nurses, often exposed to carcinogens when preparing and handling cytostatic drugs, are at especially high risk. But our results indicate that the health of oncology nurses is better than the Hungarian average, especially compared with hypertonic and type 2 diabetes nurses. However, the prevalence of iron-deficiency anaemia and different thyroid gland diseases is significantly higher in Hungarian nurses than in controls. The results suggest that iron deficiency can aggravate resistance to insulin – that is, persisting iron deficiencies may increase serum glucose levels and thus the risk of diabetes. Among the studied genetic and immune toxicology biomarkers, the incidence of CAs, SCEs and the immune suppression of T-lymphocytes was significantly higher compared with controls. These findings confirm the occupational exposure of nurses to cytostatic drugs. Thus, the introduction of stricter hygienic controls and compliance with the European Union chemical safety regulations are necessary
measures.

References
1. Stewart BW, Kleinhues P. World cancer report: multistage carcinogenesis. Lyon: WHO/IARC; 2003;
84-103.
2. IARC. Allyl compounds, aldehydes, epoxides and peroxides. Ethylene oxide (IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans). Lyon: IARC; 1988; 36: 198-226.
3. Tompa A, Major J, Jakab MG. Breast cancer cluster influenced by environmental and occupational factors among hospital nurses in Hungary.
Pathol Oncol Res 1999;5:117-122.
4. Tompa A, Jakab MG, Biró A, Magyar B, Fodor Z, Klupp T, Major J. Chemical safety and health conditions among Hungarian hospital nurses. Ann NY Acad Sci 2006;1076:635-48.
5. Jakab MG, Major J, Tompa A. Follow-up genotoxicological monitoring of nurses handling antineoplastic drugs. J Toxicol Environ Health 2001;62:307-18.
6. Public Act No. XXV on chemical safety, Hungary. Magyar Közlöny 2000;38:2058-71.
7. Hungarian Ministry of Health. 26/2000 order of the Ministry of Health. Magyar Közlöny 2000;99:6179-275.
8. NIPH. Methodological guidelines of the National Institute of Pharmacy Hungary on manufacturing and use of mixed cytostatic infusions. Gyógyszereink 2004;54:135-44.
9. Sorsa M, Hemminki K, Vainio H. Occupational exposure to anticancer drugs: potential and real hazards. Mutat Res 1985;154:135-49.
10. Carrano AV, Natarajan AT. Considerations on population monitoring using cytogenetic techniques: ICPEMC Publ. No.14. Mutat Res 1988;204:379-406.
11. Norppa H, Sorsa M, Vainio H, Grohn P, Heinonen E, Holsti L, Nordman E. Increased SCE frequencies in lymphocytes of nurses handling cytostatic agents.
Scand J Work Environ Health 1980;6:299-301.
12. Major J, Jakab MG, Tompa A. Genotoxicological investigation of hospital nurses occupationally exposed to ethylene-oxide. I: chromosome aberrations,sister chromatid exchanges, cell cycle kinetics, and UV-induced DNA synthesis in peripheral blood lymphocytes.
Environ Mol Mutagen 1996;27:84-92.
13. Biró A, Pállinger É, Falus A, Tompa A. Characterization of chemically exposed groups by immunotoxicological methods. Magyar Onkológia 2004;48:137-9.



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