With obesity and the metabolic syndrome being increasingly recognized as emerging major public health problems, biomarkers for the progression of NIDDM (non-insulin dependent diabetes mellitus, or type-2 diabetes) are sorely needed, as are quantitative endpoints for exercise and diet interventions, according to Dustin S. Hittel of the Research Center for Genetic Medicine at Children ™s National Medical Center (CNMC), Washington, D.C.

Hittel said the results of a recent study indicate the widespread and differential expression of metabolic, contractile and signal transduction proteins with training. We believe that comparative mRNA and proteomic profiling has provided us with a unique insight into the underlying metabolic crisis in chronically untrained muscle and clues as to how exercise reverses these effects.

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"The activating enzyme NQO1 is induced by several compounds. We chose DMF because of its natural origin and the fact that we could easily administer it in the diet, but there might be even better candidates for future clinical use."

Other possible inducing agents include extracts from vegetables such as broccoli and cauliflower. Similarly, there are other drugs in development that, like MMC, are activated by NQO1. If a dietary supplement is developed that successfully induces NQO1 in tumours, it is probable that it will enhance the activity of these new drugs as well.

Dr Begleiter adds, "We're hoping to start clinical trials in the near future to test the potential of this therapeutic strategy. Given the range of potential inducers of NQO1, and the increasing number of drugs that are activated by it, there's every hope we will find a successful combination."

Dr Lesley Walker, Director of Cancer Information at Cancer Research UK, says, "Mitomycin C has been used for many years to treat certain forms of cancer. This study shows that it may be possible to achieve the same anticancer effect with lower doses, which means fewer and less severe side effects for patients."

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