Modulation of chemically initiated and promoted skin tumorigenesis in CD-1 mice by dietary glucarate.

The efficacy of dietary calcium glucarate as a chemopreventative agent has been tested in the mouse skin tumorigenesis system. Skin tumorigenesis was initiated in mice of the CD-1 strain with 7,12-dimethylbenz(a)anthracene (DMBA), then promoted with twice weekly applications of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) for 13 weeks. The mice were fed a regular chow diet, or a chow diet fortified with calcium glucarate (128 mmol/kg diet), or with equimolar calcium as calcium gluconate (negative calcium control). When mice were fed calcium glucarate throughout both the initiation and promotion phases papilloma formation was inhibited by over 30%. Transfer of these DMBA-initiated, TPA promoted CD-1 mice to chow diet after 13 weeks on the calcium glucarate-supplemented diet, resulted in an increase in the number of skin papillomas within 3 weeks to the level of those seen in control animals maintained exclusively on the chow diet. When calcium glucarate feeding was restricted to either the initiation or promotion phases, papilloma formation was inhibited by 25%. Dietary calcium gluconate had no effect on papilloma formation in the CD-1 mouse system, but increased the calcium concentration in the skin to the same extent as that of calcium glucarate. The data indicate that the elevation of the normally low levels of glucarate in the body through supplementation, results in a marked alteration in the retention, activity and/or metabolism of xenobiotics.