Abstract: Biological Effect Monitoring in Peripheral Blood Lymphocytes from Subjects Occupationally Exposed to Antineoplastic Drugs: Assessment of Micronuclei Frequency: Milena

Antineoplastic drugs (ANPDs) are a heterogeneous group of chemicals that include alkylating agents (e.g., cyclophosphamide, melphalan, chlorambucil), antimetabolites (e.g., thioguanine, 5-fluorouracil, methotrexate), antibiotics (e.g., doxorubicin), mitotic spindle inhibitors (e.g., vincristine), hormones (e.g., diethylstilbestrol, free radical generators (e.g., bleomycin) and topoisomerase inhibitors (e.g., irinotecan, etoposide). These drugs are often used in combination to achieve synergistic effects on tumor cells resulting from their differing modes of action. However, most if not all of these chemical agents are generally nonselective and, along with tumor cells, normal cells may undergo cytotoxic/genotoxic damage . Despite their therapeutic and beneficial effects in cancer patients with life-threatening conditions, both acute/short-term and chronic/long-term adverse effects are associated with ANPD treatment. Among the latter, several studies have pointed to the occurrence of secondary tumors in cancer patients as a result of their exposure to ANPDs. Based on side effects in cancer patients and animal carcinogenicity data, as well as on results from in vitro studies, the International Agency for Research on Cancer (IARC) currently lists 11 agents and 2 combined therapies in clinical use in Group 1 (i.e., human carcinogens, Abstract: Biological Effect Monitoring in Peripheral Blood Lymphocytes from Subjects Occupationally Exposed to Antineoplastic Drugs: Assessment of Micronuclei Frequency: Milena VILLARINI, et al. Department of Medical-Surgical Specialties and Public Health (Section of Public Health), University of Perugia, Italy—Objectives: Antineoplastic drugs (ANPDs) are widely used in the treatment of cancer and some nonneoplastic diseases. However, most if not all of these chemical agents are generally nonselective and, along with tumor cells, normal cells may undergo cytotoxic/genotoxic damage. Italian pharmacists and nurses occupationally exposed to ANPDs during their normal work routines were monitored to evaluate biological effects (i.e., cytogenetic damage) eventually associated with exposure. The subjects were also monitored for primary, oxidative and excision repaired DNA damage as evaluated by comet assay (published data). In the present paper, we present the results obtained with the cytokinesis-block micronucleus (CBMN) test. Methods: The CBMN test in peripheral blood lymphocytes was applied because of its ability to detect both clastogenic and aneugenic effects, and because it has recently been reported that micronuclei (MNs) are predictive of cancer risk in human populations. In this study, the evaluation of MN frequency was carried out using the CBMN test in the absence or in the presence of the DNA repair inhibitor Ara-C (cytosine arabinoside). Results: No significant difference was observed for MN frequency comparing nurses handling ANPDs (exposed subjects) and controls; no correlations were found between job seniority, age, smoking habits Biological Effect Monitoring in Peripheral Blood Lymphocytes from Subjects Occupationally Exposed to Antineoplastic Drugs: Assessment of Micronuclei Frequency