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- Cytostatics occupational exposure: genotoxic effects assessmentPublication . Ladeira, Carina; Viegas, Susana; Carolino, Elisabete; Gomes, M. C.; Brito, MiguelThe use of cytostatics drugs in anticancer therapy is increasing. Health care workers can be occupationally exposed to these drugs classified as carcinogenic, mutagenic or teratogenic. Workers may be exposed to this drug, being in the hospital settings the main focus dwelled upon the pharmacy, and nursing personnel. Although the potential therapeutic benefits of hazardous drugs outweigh the risks of side effects for ill patients, exposed health care workers can have the same side effects with no therapeutic benefit. The exposure to these substances is epidemiologically linked to cancer and nuclear changes detected by the cytokinesis-block micronucleus test (CBMN). This method is extensively used in molecular epidemiology, since it determines several biomarkers of genotoxicity, such as micronuclei (MN), which are biomarkers of chromosomes breakage or loss, nucleoplasmic bridges (NPB), common biomarkers of chromosome rearrangement, poor repair and/or telomeres fusion, and nuclear buds (NBUD), biomarkers of elimination of amplified DNA.
- Application of alkaline comet assay in human biomonitoring for genotoxicity: a study on occupational exposure to cytostaticsPublication . Ladeira, Carina; Viegas, Susana; Carolino, Elisabete; Gomes, M. C.; Brito, MiguelThe use of cytostatics drugs in anticancer therapy is increasing. Health care workers can be occupationally exposed to these drugs classified as carcinogenic, mutagenic or teratogenic. Cytostatics drugs are a heterogeneous group of chemicals widely used in the treatment of cancer, nevertheless have been proved to be also mutagens, carcinogens and teratogens. Workers may be exposed to this drug, being in the hospital settings the main focus dwelled upon the pharmacy, and nursing personnel. Alkaline comet assay is one of the most promising short-term genotoxicity assays for human risk assessment, being recommended to monitor populations chronically exposed to genotoxic agents. DNA glycosylase (OGG1) represents the main mechanism of protecting the integrity of the human DNA with respect to 8-OHdG, the most well studied biomarker of oxidative damage.
- Human nutrition, DNA damage and cancer: a reviewPublication . Ladeira, Carina; Gomes, M. C.; Brito, MiguelDietary habits are recognized to be an important factor influencing cancer risk and tumour behaviour. Diet can influence cancer development in several ways, as direct action of carcinogens in food can damage DNA, and some diet components (macro or micronutrients) can block or induce enzymes involved in activation or deactivation of carcinogenic substances. Moreover, inadequate intake of some molecules involved in DNA synthesis, repair or methylation can influence mutation rate or changes in the gene expression mechanism. From a mechanistic view of carcinogenesis, food mutagens are classified as genotoxic and non-genotoxic. Genotoxic agents cause DNA damage resulting in gene point mutations, deletions, and insertions, recombination, rearrangements, and amplifications, as well as chromosomal aberrations. Non-genotoxic agents are less distinctively defined in terms of their modes of action, but they are presumed to indirectly affect cell proliferation as tumours promoters, with or without accompanying chronic cell damage. Another mechanism that diet can influence DNA mutation, and consequently cancer risk, is energy balance and growth rates since nutrition will influence hormone levels and growth factors that will influence the rate of cell division, cell cycling and consequently influence time for DNA repair and/or replication of DNA lesions. Nutritional genomics studies the functional interaction of food and its components, macro and micronutrients, with genome at molecular, cellular, and systemic level. One of the goals is to identify biomarkers that will provide better guidance on the relationship between nutrition and health. Also relevant are the implications of genetic polymorphisms and their role in the interaction between diet, environmental factors, lifestyles, and cancer risk. The recognition of the importance of adequate dietary levels of micronutrients in maintaining genomic stability is very significant because the latter is also affected by inadequate nutrient intakes, such as lack of vitamins A, D, E, folate, selenium, and others.
- Biomonitorization in hospital settings with cytostatics occupational exposurePublication . Ladeira, Carina; Viegas, Susana; Carolino, Elisabete; Gomes, M. C.; Brito, MiguelExposure in a hospital setting is normally due to the use of several antineoplastic drugs simultaneously. Nevertheless, the effects of such mixtures at the cell level and on human health in general are unpredictable and unique due to differences in practice of hospital oncology departments, in the number of patients, protection devices available, and the experience and safety procedures of medical staff. Health care workers who prepare or administer hazardous drugs or who work in areas where these drugs are used may be exposed to these agents in the air, on work surfaces, contaminated clothing, medical equipment, patient excreta, and other surfaces. These workers include specially pharmacists, pharmacy technicians, and nursing personnel. Exposures may occur through inhalation resulting from aerosolization of powder or liquid during reconstitution and spillage taking place while preparing or administering to patients, through Cytokinesis-block micronucleus test (CBMN) is extensively used in biomonitoring, since it determines several biomarkers of genotoxicity, such as micronuclei (MN), which are biomarkers of chromosomes breakage or loss, nucleoplasmic bridges (NPB), common biomarkers of chromosome rearrangement, poor repair and/or telomeres fusion, and nuclear buds (NBUD), biomarkers of elimination of amplified DNA.
- Assessment of genotoxic effects in nurses handling cytostatic drugsPublication . Ladeira, Carina; Viegas, Susana; Pádua, Mário; Gomes, Mário; Carolino, Elisabete; Gomes, M. C.; Brito, MiguelSeveral antineoplastic drugs have been classified as carcinogens by the International Agency for Research on Cancer (IARC) on the basis of epidemiological findings, animal carcinogenicity data, and outcomes of in vitro genotoxicity studies. 5-Fluorouracil (5-FU), which is easily absorbed through the skin, is the most frequently used antineoplastic agent in Portuguese hospitals and therefore may be used as an indicator of surface contamination. The aims of the present investigation were to (1) examine surface contamination by 5-FU and (2) assess the genotoxic risk using cytokinesis-block micronucleus assay in nurses from two Portuguese hospitals. The study consisted of 2 groups: 27 nurses occupationally exposed to cytostatic agents (cases) and 111 unexposed individuals (controls). Peripheral blood lymphocytes (PBL) were collected in order to measure micronuclei (MN) in both groups. Hospital B showed a higher numerical level of contamination but not significantly different from Hospital A. However; Hospital A presented the highest value of contamination and also a higher proportion of contaminated samples. The mean frequency of MN was significantly higher in exposed workers compared with controls. No significant differences were found among MN levels between the two hospitals. The analysis of confounding factors showed that age is a significant variable in MN frequency occurrence. Data suggest that there is a potential genotoxic damage related to occupational exposure to cytostatic drugs in oncology nurses.