Oxidative stress-related mechanisms are associated with xenobiotics exerting excess toxicity to Fanconi anemia cells.
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.
Italian National Cancer Institute, Pediatric Oncology Research Center, Mercogliano, Italy. gbpagano@tin.it
Giovanni
G
Pagano
Paola
P
Manini
Debasis
D
Bagchi
D002274:Carcinogens, Environmental / Q000633:toxicity*; D018929:Cell Culture Techniques; D002857:Chromium / Q000633:toxicity*; D005199:Fanconi Anemia / Q000503:physiopathology*; D006801:Humans; D018384:Oxidative Stress; D010641:Phenotype; D015262:Xenobiotics / Q000633:toxicity*
D002274:Carcinogens, Environmental; D015262:Xenobiotics; D002857:Chromium; C074702:chromium hexavalent ion