Fig. 3.

NAC-mediated protection against UV-induced oxidative stress suggests potential utility of novel paradigm for melanoma chemoprevention. A, Two similar-appearing nevi were removed from 19 patients immediately prior to, and 3 h following ingestion of 1200 mg NAC. Fragments of each nevus were either untreated or UV-irradiated (4000 J/m²), then cultured for either 24 h (8 patients) or 48 h (11 patients). GSH content (normalized to nevus weight) was determined for each nevus fragment. B, Data expressed as percent UV-induced GSH depletion (UV-treated vs. untreated) in fragments of pre-drug nevi (open bars) and post-drug nevi (filled bars) from each patient. For nevi cultured 24 h, there was protection (ie. less GSH depletion) in 3/8 patients (left panel); for nevi cultured 48 h, there was protection in 6/11 patients. C, Schematic illustrating proposed novel paradigm for melanoma chemoprevention based on these pilot studies. Patients could take NAC in anticipation of sun exposure, to protect their nevi and other skin melanocytes from UV-induced oxidative stress (lower panel), and reduce their long-term risk of melanoma if applied over many years and sun exposures. This approach would circumvent the major pitfalls of conventional chemoprevention (upper panel) by timing drug administration with activation of a relevant oncogenic pathway, and episodic drug ingestion would avoid potential deleterious effects that may be associated with chronic use of any drug.