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Dietary Depletion of Vit E/A Inhibits Mmmry Tumor Growth

Dietary depletion of vitamin e and vitamin a inhibits mammary tumor growth and metastasis in transgenic mice.

Albright CD, Salganik RI, Van Dyke T.

Department of Nutrition, School of Public Health, and. Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina, Chapel Hill, NC 27599.

We showed previously that dietary antioxidant depletion enhances tumor reactive oxygen species (ROS) and apoptosis, resulting in a reduction in brain tumor size in the TgT(121) transgenic mouse model, a nonmetastatic tumor model.

Here, in a transgenic mouse model of mammary tumorigenesis with defined rates of tumor growth and lung-targeted metastasis, we determined the ability of dietary antioxidant depletion to inhibit tumor growth and metastasis.

Compared with control mice fed a standard diet, antioxidant-depleted mice exhibited tumor-targeted generation of ROS manifested by increased levels of oxidatively modified DNA/RNA (8- hydroxy-2'-deoxyguanine, 8-hydroxyguanine) and lipid peroxidation (4-hydroxy-2-nonenal) in primary and metastatic tumor foci.

In addition to increased tumor-targeted ROS, the number of apoptotic cells was increased approximately 500% (P < 0.01) and terminal dUTP nucleotide DNA end-labeling-positive cells 200% (P < 0.01) in mice fed the antioxidant-depleted diet, whereas the percentage of tumor cells undergoing mitosis was >50% lower than in controls (P < 0.01).

The proportional distribution of small (<1.5 cm) and large (>/==" BORDER="0">1.5 cm) primary mammary tumors differed.

The mice fed the antioxidant-depleted diet had more small primary tumors (P <0.05) and fewer large primary tumors (P < 0.05). Importantly, they also had fewer lung metastatic tumor foci compared with mice fed the control diet (4.5 +/- 1.3 vs. 15.8 +/- 8.5 foci/lung, P < 0.01).

These findings may be important in understanding the role of dietary antioxidant vitamins in tumor growth and metastasis.

J Nutr. 2004 May;134(5):1139-44.

Ann's NOTE: We asked Kedar Prasad, PhD, Center for Vitamin and Cancer Research, Dept. of Radiology, University of Colorado,Colorado Health Science Ctr., to comment.

He sent us a proof of his newest paper as a 'proof'.

Title: "Antioxidants in cancer care:when and how to use them as an adjunct to standard and experimental therapies". The sections include: Types of anti-oxidants and their derivatives, doses and treatment schedules; Use of anti-oxidants by cancer patients: current status; Effects of anti-oxidations on cancer cells; Clinical studies with multiple dietary anti-oxidants in combination with standard therapy; Proposed micronutrient protocols as an adjunct to standard cancer therapy; Expert opinion; Five-year view; Key issues (total of 12 pages).

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