UV exposure inhibits intestinal tumor growth and progression to malignancy in intestine-specific Apc mutant mice kept on low Vitamin D diet

Abstract

Mortality from colorectal cancer increases with latitude and decreases with ambient UV radiation. We investigated whether moderate UV dosages could inhibit intestinal tumor development and whether this corresponded with UV-induced vitamin D. FabplCre;Apc 15lox/+ mice, which develop intestinal tumors, and their parents were put on a vitamin D-deficient diet. Next to a control group, one group was vitamin D supplemented and another one group was daily UV irradiated from 6 weeks of age. Vitamin D statuses after 6 weeks of treatment were markedly increased: mean ± SD from 7.7 ± 1.9 in controls to 75 ± 15 nmol/l with vitamin D supplementation (no gender difference), and to 31 ± 13 nmol/l in males and 85 ± 17 nmol/l in females upon UV irradiation. The tumor load (area covered by tumors) at 7.5 months of age was significantly reduced in both the vitamin D-supplemented group (130 ± 25 mm 2, p = 0.018) and the UV-exposed group (88 ± 9 mm 2, p < 0.0005; no gender differences) compared to the control group (202 ± 23 mm 2). No reductions in tumor numbers were found. Only UV exposure appeared to reduce progression to malignancy (p = 0.014). Our experiments clearly demonstrate for the first time an inhibitory effect of moderate UV exposure on outgrowth and malignant progression of primary intestinal tumors, which at least in part can be attributed to vitamin D. What's new Mortality from colorectal cancer decreases as ambient levels of UV radiation increase, suggesting that UV exposure is critical to the prevention of the disease. This study demonstrates the biological plausibility in mice of a causal relationship between moderate chronic UV irradiation or vitamin D supplementation and an impairment of outgrowth of primary intestinal cancer. While both UV irradiation and vitamin D supplementation decreased the overall area covered by tumors, only UV exposure inhibited malignant progression.