D. James Morré

Differential response of the NADH oxidase of plasma membranes of rat liver and hepatoma and HeLa cells to thiol reagents

NADH oxidase activity of plasma membranes from rat hepatoma and HeLa cells responded to thiol reagents in a manner different from that of plasma membranes of liver. Specifically, the NADH oxidase activity of plasma membranes of HeLa cells was inhibited by submicromolar concentrations of the thiol reagentsp-chloromercuribenzoate (PCMB),N-ethylmaleimide (NEM), or 5,5′-dithiobis-(2-nitrophenylbenzoic acid) (DTNB), whereas that of the rat liver plasma membranes was unaffected or stimulated over a wide range of concentrations extending into the millimolar range. With some hepatoma preparations, the NADH oxidase activity of hepatoma plasma membranes was stimulated rather than inhibited by PCMB, whereas with all preparations of hepatoma plasma membranes, NEM and DTNB stimulated the activity. In contrast, NADH oxidase activity of rat liver plasma membrane was largely unaffected over the same range of PCMB concentrations that either stimulated or inhibited with rat hepatoma or HeLa cell plasma membranes. Dithiothreitol and glutathione stimulated NADH oxidase activity of plasma membranes of rat liver and hepatoma but inhibited that of HeLa plasma membranes. The findings demonstrate a difference between the NADH oxidase activity of normal rat liver plasma membranes of rat hepatoma and HeLa cell plasma membranes in addition to the differential response to growth factors and hormones reported previously (Brunoet al., 1992). Results are consistent with a structural modification of a NADH oxidase activity involving thiol groups present in plasma membranes of rat hepatoma and HeLa cells but absent or inaccessible with plasma membranes of rat liver.

Early Detection: An Opportunity for Cancer Prevention Through Early Intervention

Cancer is the second leading disease cause of death in the United States. A group of more than 100 different and distinctive diseases, cancer may involve any tissue of the body. Estimates are that there were over 1.5 million cases in 2010 in the United States alone. Only a small fraction (less than 20%) of cancers are diagnosed at a localized stage where curative therapy is effective. Most cancers are diagnosed only after the primary tumor has already metastasized so that chemotherapy is required for treatment. Hence, early detection is a favored opportunity to reduce cancer mortality. By detecting cancer in its very earliest stages when perhaps only a small number of cells are present, it is possible that early intervention will be effective in preventing further development of the incipient cancer thereby resulting in what might be viewed as curative prevention.