Effect of Calcium D-Glucarate on Expression of Ki-ras and p53 genes in Benzo(alpha)Pyrene-Induced Lung Lesions in Female A/J Mice Walaszek, Z, Szemraj, J, Hanausek, M, Narog, M, Kordari, E, Barnett, K, Farrell, D, and Slaga, T.J. AMC Cancer Research Center, Denver, CO. Our previous studies have shown that D-glucaro-1,4-lactone (1-4-GL), and its precursors such as calcium D-glucarate (CG), inhibit chemically induced tumor-igenesis in rodents, in part by inhibiting the enyme Beta-glucoridase (BG). 1-4-GL increases detoxification of carcinogens and tumor promoters by preventing hydrolysis of their glucuronides. The protective mechanism conferred by BG depletion operates, in part, through a reduction in the covalent binding of procarcinogen metabolites to DNA. Specifically, pre-initiation treatment with CG reduced the in vivo binding of benzo(alpha) pyrene (BP) to DNA of the lung in A/HeJ or A/J mice by 70%. Yet for both pre- and post-initation treatment of A/HeJ or A/J mice, CG significantly decreased the number of BP-induced lung adenomas. Our recent study provided evidence on the ability of CG to inhibit cell proliferation during post-initiation stages of lung tumorigenesis in A/J mice. In the present study, CG was continually fed to the A/J mice in AIN-93G diet (4% w/w) beginning 2 weeks after the second dose of the two 3 mg doses of BP, i.e. prior to the completion of the DNA adducts removal. The animals were sacrificed 16 weeks after the second dose of BP. Since BP metabolites were known to mutate the Ki-ras and p53 genes in BP-induced lung lesions, we investigated the expression and mutations of these genes using immunohistochemistry and or PCR and sequence analysis. Post-initiation treatment with CG markedly reduced the number of BP-induced lung lesions with mutated Ki-ras and p53 genes, i.e. by 60% and 50% respectively. We conclude that CG may inhibit promotion and progression of lung tumorigenesis in A/J mice by facilitation DNA adduct removal and suppressing mutagenesis in BP-induced lesions. Ann's NOTE: Some cancer patients take calcium D-glucarate in dietary supplement form. The above is an (as yet) unpublished study in animals only, but seems to indicate that these animals benefited by ingesting the substance. Reduction of the number of tumor lesions and possibly other meaningful results were shown. As always, it would be really nice to see human trials of the use of dietary supplements acting in concert. Actually animal studies of beneficial substances in concert, would be a good step too. 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.