Potential role of D-glucaric acid in lung cancer prevention Zbigniew Walaszek, Peter C. Raich, Margaret Hanausek, Janusz Szemraj, Maciej Narog, Erick Spears, Thomas J. Slaga AMC Cancer Research Center, Denver, CO. The investigators have previously shown that calcium D-glucarate, found in many fruits and vegetables as D-glucaric acid (GA), is able to inhibit benzo[a]pyrene (BP)-induced mouse lung tumorigenesis by facilitating DNA-adduct removal and suppressing cell proliferation and K-ras mutations. GA is an apparently non-toxic, natural compound, produced in small amounts by mammals, including humans. One of its derivatives is the potent â-glucuronidase (âG) inhibitor D-glucaro-1,4-lactone. The latter increases detoxification of some carcinogens and tumor promoters by preventing hydrolysis of their glucuronides. Our Phase I clinical trial was undertaken in order to explore the potential role of GA supplementation in the prevention of lung cancer in current tobacco smokers. Initially, blood levels of GA and âG were determined at baseline. In addition, peripheral blood lymphocytes and sputum specimens were collected for restriction enzyme analysis of K-ras mutations at codon 12. We have isolated genomic DNA from the lymphocyte fraction of the blood and from sputum obtained from male (n=8) and female smokers (n=15) and male (n=20) as well as female non-smokers (n=19). We found mutated K-ras, an oncogene linked to lung cancer, in the baseline lymphocytes of three male smokers (37.5%). In two of eight male smokers (25%) and in one out of fifteen female smokers (6.6%), mutated K-ras was also found in the DNA isolated from sputum. Direct sequencing of PCR products with K-ras mutations revealed the presence of the following mutations of K-ras codon 12: GGT-TGT and GGT-GAT. No K-ras mutations were found in the specimens obtained from non-smokers. The baseline D-glucaric acid level in the blood of male smokers with mutated K-ras was significantly lower (i.e., 1.0 ±0.15 µM, p<0.005) than in other male smokers (1.42 ± 0.33 µM). Overall, D-glucaric acid levels were 29% lower in male smokers, as compared to male non-smokers (1.83 ± 0.26 µM; p<0.005). A similar trend was observed in female subjects. No correlation was observed between GA and âG levels. In conclusion, the recent findings support our hypothesis that D-glucaric acid deficiency may correlate with K-ras mutations and may indicate a higher risk for lung cancer. Calcium D-glucarate supplementation, therefore, has potential for reducing the risk of lung cancer development in tobacco smokers. Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.