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Giovanni Pagano,¹ Paola Manini,² and Debasis Bagchi³

¹Italian National Cancer Institute, Pediatric Oncology Research Center, Mercogliano, Italy; ²Department of Organic Chemistry and Biochemistry, Federico II Naples University, Naples, Italy; ³Department of Pharmacy Sciences, Creighton University School of Pharmacy and Health Professions, Omaha, Nebraska, USA

Abstract
An extensive body of evidence has demonstrated the sensitivity of Fanconi anemia (FA) cells to redox-active xenobiotics, such as mitomycin C, diepoxybutane, cisplatin, and 8-methoxypsoralen plus ultraviolet irradiation, with toxicity mechanisms that are consistent with a deficiency of FA cells in coping with oxidative stress. A recent study has reported on excess sensitivity of FA complementation A group cells to chromium VI [Cr(VI) ] toxicity, by postulating that a deficiency in Cr-DNA cross-link removal by FA cells and formation of Cr(VI) -associated cross-links may be the mechanism of Cr(VI) -induced cytotoxicity. However, the report failed to demonstrate any enhanced Cr uptake or, especially, any increase in Cr-DNA adducts. Thus, well-established findings on Cr(VI) -induced oxidative stress may explain excess sensitivity of FA cells to Cr(VI) in terms of its inability to cope with the Cr(VI) -induced prooxidant state. Key words: chromium, cisplatin, diepoxybutane, DNA adducts, Fanconi anemia, 8-hydroxy-2´-deoxyguanosine, 8-methoxypsoralen, mitomycin C, oxidative stress. Environ Health Perspect 111:1699-1703 (2003) . doi:10.1289/ehp.6229 available via http://dx.doi.org/ [Online 12 June 2003]

Address correspondence to G. Pagano, Istituto Nazionale Tumori, Centro Ricerche in Oncologia Pediatrica, via Ammiraglio Bianco, I-83013 Mercogliano (AV) , Italy. Telephone: 39-335-6910060. Fax: 39-081-3031141. E-mail: gbpagano@tin.it

We thank F. Panzeri for skillful assistance.

G.P. participated in this study through the European Research on Oxidative Stress (EUROS) Project ; the study was supported by the European Commission DGXII (contract BMH4-CT98-3107) and by the Italian Association for Fanconi Anemia Research.

The authors declare they have no conflict of interest.

Received 22 January 2003 ; accepted 12 June 2003.