The regulation of estrogenic and antiestrogenic effects by selective estrogen receptor modulators (SERMs) provides the basis for use in long-term therapy in cancer chemoprevention and postmenopausal osteoporosis. However, the evidence for carcinogenic properties within this class requires study of potential pathways of toxicity. There is strong evidence for the elevation of cellular levels of NO in tissue treated with SERMs, including the benzothiophene

NO is produced endogenously from arginine by the action of NO synthase, and exogenously by nitrovasodilators, including organic nitrates and nitrites. NO has been proposed as a cytotoxic and cytoprotective agent. There is strong evidence that NO acts as an apparent antioxidant in inhibiting lipid peroxidation, via chain termination, and interestingly lipid nitrates and nitrites have been proposed to be products of this chain termination. Both pro-

The important biological secondary messenger NO can be generated from exogenous nitrovasodilators and NO donors. Nitrate esters are nitrovasodilators and NO mimetics, believed to be biotransformed to NO in vivo. On the basis of a mechanistic hypothesis, nitrates have been synthesized that release NO at significant rates in neutral aqueous solution in the presence only of added thiol. The novel masked -mercaptonitrates reported (SS-nitrates), provide

Evidence exists for both the cytoprotective and cytotoxic effects of the endogenous chemical messenger, nitric oxide (NO). Oxidative damage to lipid constituents of biological membranes is implicated in many disease states, with growing evidence for: a causative role for Fe in lipid peroxidation; and links between disruption of Fe homeostasis, Fe-induced oxidative stress, and neurodegeneration. Peroxynitrite may induce peroxidation, but NO itself