Toxicology Letters 197 (2010) 61–68 Contents lists available at ScienceDirect Toxicology Letters journal homepage: www.elsevier.com/locate/toxlet Doxorubicin can penetrate nitrile gloves and induces apoptosis in keratinocytes cell lines Mariarosaria Boccellino a , Paola Pedata b , Loredana Castiglia b , Raffaele La Porta a , Maria Pieri b , Lucio Quagliuolo a , Antonio Acampora c , Nicola Sannolo b,∗ , Nadia Miraglia b a Department of Biochemistry and Biophysics, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy b Department of Experimental Medicine – Occupational Medicine, Hygiene and Industrial Toxicology Section, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy c Department of Public Medicine and Social Safety, University of Naples “Federico II”, Via Pansini 5, 80131 Naples, Italy article info Article history: Received 24 February 2010 Received in revised form 27 April 2010 Accepted 29 April 2010 Available online 7 May 2010 Keywords: Skin Doxorubicin Apoptosis Occupational exposure Gloves permeability abstract Doxorubicin (DOXO) is an anthracycline antibiotic which is used in the treatment of human malignancies such as leukemia, lymphoma and a number of solid tumors, particularly breast cancer. Anthracyclines have been reported to contaminate chemotherapy workstation surfaces as well as other workplaces surfaces. The occupational exposure to these drugs could occur in hospitals, for nurses involved in anthracyclines preparation and administration, in chemical industries during the commercial formulate syntheses, and in analytical laboratories. Numerous studies investigated cutaneous effects related to DOXO administration, on the contrary few literature data are available about effects on the skin due to the direct contact with the drug. The present study investigated the DOXO permeability of three commercially available gloves’ types used to protect skin in occupational contexts, as well as the effects of DOXO on human keratinocyte cell line (HaCaT). The results suggest that the DOXO permeability of gloves depends not only on glove material but also on DOXO solutions’ pH, in fact nitrile gloves can be penetrated by acid solutions, while neither natural rubbers nor nitrile gloves are permeable to neutral solutions. Moreover, DOXO solutions, even at low concentration, cause apoptosis in epithelial cells, through activation of intrinsic pathway p53- independent. © 2010 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Doxorubicin (DOXO) belongs to a family of anthracycline antibiotics first isolated from Streptomyces peucetius. Anthracy- clines show a broad spectrum of antitumor activity against acute leukemias, Hodgkin’s and Non-Hodgkin’s lymphomas, breast can- cer, lung cancer, and sarcomas (Blum and Carter, 1974). As a consequence, anthracyclines are widely used as antiblastic agents, even though, numerous secondary effects were observed in patients under treatment, such as nausea, vomiting, alope- cia, stomatitis, and myelosuppression. Furthermore, anthracyclines long-term clinical use is limited by the development of a cumulative dose-related cardiotoxicity, characterized by myocyte damage and myofibrillar loss. Moreover, the International Agency for Research on Cancer (IARC) classifies DOXO (adriamycin = doxorubicin syn- onymous) in Group 2A, as probably carcinogenic to humans (Dorr and Von Hoff, 1994; Simmons et al., 2008; IARC, 1990). ∗ Corresponding author. Tel.: +39 081 5665900; fax: +39 081 5665898. E-mail addresses: paola.pedata@unina2.it, ppedata@libero.it (N. Sannolo). Toxic side-effects might be explained by a non-selective action mechanism, acting both on healthy and cancer cells, through DNA intercalation and strand breakage, inhibition of topoisomerase II, formation of metal complexes with iron or copper, and free radicals formation (Dorr and Von Hoff, 1994; Sessa et al., 2007). While the appearance of toxic effects is considered acceptable in patients in view of therapeutic benefits, the occurrence of primary tumors in healthy subjects handling them, such as healthcare ser- vice teams, cannot be acceptable (Fuchs et al., 1995). Anthracyclines have been reported to contaminate chemotherapy workstation sur- faces as well as other workplaces surfaces (Roberts et al., 2006; Connor, 2006; Castiglia et al., 2008), and the occupational expo- sure to these drugs could occur in hospitals, for nurses involved in anthracyclines preparation and administration, in chemical indus- tries during the commercial formulate syntheses, and in analytical laboratories. Inhalation and cutaneous exposures represent the main routes of penetration of toxic agents in occupationally exposed people. When dermal exposure is considered, beyond systemic effects, also local effects on epithelial cells should be taken into account. Numerous studies investigated cutaneous effects related to DOXO 0378-4274/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.toxlet.2010.04.026