The role of CSA in the response to oxidative DNA damage in human cells.

Cockayne syndrome (CS) is a rare genetic disease characterized by severe growth, mental retardation and pronounced cachexia. CS is most frequently due to mutations in either of two genes, CSB and CSA. Evidence for a role of CSB protein in the repair of oxidative DNA damage has been provided recently. Here, we show that CSA is also involved in the response to oxidative stress. CS-A human primary fibroblasts and keratinocytes showed hypersensitivity to potassium bromate, a specific inducer of oxidative damage. This was associated with inefficient repair of oxidatively induced DNA lesions, namely 8-hydroxyguanine (8-OH-Gua) and (5'S)-8,5'-cyclo 2'-deoxyadenosine. Expression of the wild-type CSA in the CS-A cell line CS3BE significantly decreased the steady-state level of 8-OH-Gua and increased its repair rate following oxidant treatment. CS-A cell extracts showed normal 8-OH-Gua cleavage activity in an in vitro assay, whereas CS-B cell extracts were confirmed to be defective. Our data provide the first in vivo evidence that CSA protein contributes to prevent accumulation of various oxidized DNA bases and underline specific functions of CSB not shared with CSA. These findings support the hypothesis that defective repair of oxidative DNA damage is involved in the clinical features of CS patients.

Neutrophilic eccrine hidradenitis secondary to topotecan.

BACKGROUND: Neutrophilic eccrine hidradenitis (NEH) is a self-restricted inflammatory condition, usually secondary to chemotherapeutic agents and less frequently to other drugs such as zidovudine or various infections. NEH clinical features include erythematous, occasionally painful nodules and plaques. Histological examinations reveal neutrophilic infiltrates and degeneration of eccrine glands. METHODS: A 45-year-old female was treated with topotecan and colony-stimulating factor for ovarian cancer. RESULTS: The erythematous and slightly pruritic plaques on the upper and lower limbs and ear lobes appeared approximately 1 week after chemotherapy and spontaneously subsided in about 10 days, only to recur after the next drug dose. A skin biopsy revealed NEH; all skin cultures were negative. CONCLUSION: It is believed that this patient developed topotecan-induced NEH; this relationship with therapy rather than the underlying disease rules out a paraneoplastic reaction, and negative cultures excluded infectious causes. In addition, since skin lesions recurred after CSF was discontinued, this agent was not involved. Studies relating NEH to topotecan, a topoisomerasa I inhibitor, have not reported such an event in the literature.