Abstract 944: Preventive effects of UV radiation and dietary vitamin D on autochthonous murine mammary tumors

Abstract

Abstract Epidemiologic studies support an inverse correlation between solar UV radiation and breast cancer incidence and mortality, a matter of some concern in a society being urged to avoid sun exposure. We assessed directly whether UV radiation of skin has any preventive effect on mammary tumor carcinogenesis in the C3(1)SV40 Tag transgenic mouse. Mice fed diets depleted of vitamin D (+ rescue minerals) were treated with 0 [group A] or 350mJ/cm2 UV 3 times a week without [Group B] or with [Group C] topical 7-dehydrocholesterol, the precursor of cutaneous vitamin D3. Control mice were fed an otherwise identical diet but containing normal levels of vitamin D (1,000IU/kg + rescue minerals) [Group D]. We also fed mice a separate diet containing high (20,000IU/kg) [Group E] or normal (1,000IU/kg) [Group F] vitamin D. We examined mice and excised all palpable tumors (“lumpectomies”) every two weeks at ages 16-28 weeks. Blood was collected at the end of the study. Analyses were performed using Krusskal Wallis test, Mann Whitney test, Spearman's test, life table survival analysis, and log rank test. Circulating 25-hydroxyvitamin D3 (25D3) levels in 59 mice, measured in ng/mL [median (interquartile range)] in groups A-F were 3.0(1.0) 34.0(26.3), 26.0(18.0), 28.0(13.0), 121.0(82.5), and 42.0(15.5), respectively (p<0.001). We found no significant correlation among groups between 25D3 levels and tumor number, mean size, or total tumor volume/mouse. Mice fed the vitamin D depleted diet had a tumor burden that was reduced by UV radiation or by addition of dietary vitamin D, and UV-treated mice had a longer tumor free survival than did the D-depleted mice not so treated. By contrast, the high vitamin D diet, despite tripling the circulating 25D3 level, by comparison to the control diet did not influence mammary tumor number or size or tumor free survival. We interpret these data to suggest that although UV can inhibit development of autochthonous murine mammary tumors, the failure of tumor development to correlate strictly with circulating 25OH D3 levels suggests that its effects may be mediated in part by non-obvious pathways and/or that the anti-mammary cancer effects of vitamin D may plateau. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 944.