TY - JOUR
T1 - High Oral Vitamin D3 Intake Does Not Protect Against UVR-induced Squamous Cell Carcinoma in Mice
AU - Lerche, Catharina M
AU - Pinto, Fernanda E
AU - Philipsen, Peter A
AU - Bech, Elisabeth S
AU - Jakobsen, Jette
AU - Haedersdal, Merete
AU - Wulf, Hans Christian
N1 - Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
PY - 2022/10
Y1 - 2022/10
N2 - BACKGROUND/AIM: The effect of vitamin D on skin carcinogenesis is unclear. Vitamin D derivatives may protect against ultraviolet radiation (UVR)-induced DNA damage, immune suppression, and skin carcinogenesis. However, some epidemiological studies have reported an increased incidence of skin cancer associated with high serum vitamin D levels. We investigated the effect of vitamin D supplementation on serum, skin, and tumor vitamin D levels and on skin cancer development in hairless immunocompetent mice.MATERIALS AND METHODS: Female C3.Cg-Hrhr/TifBomTac immunocompetent mice (n=125) were randomly separated into five groups. Two groups received a high vitamin D3 diet (4.5 μg/day/mouse). One group received a medium vitamin D3 diet (2.3 μg/day/mouse). Two groups received a standard diet (0.045 μg/day/mouse). Three standard erythema doses of UVR were given three times per week to three groups.RESULTS: Animals on a high vitamin D3 diet had ~150-fold higher serum vitamin D3 levels (p=0.00016) and 3-fold higher serum 25-hydroxyvitamin D3 [25(OH)D3] levels (p=0.00016) than those on a standard diet. For mice on the medium vitamin D3 diet, serum vitamin D3 and 25(OH)D3 levels were 18-fold and 2.3-fold higher than for the standard diet, respectively (p=0.00016). All UVR-exposed mice developed tumors. Vitamin D3 levels were lower in the tumor than the skin (p<0.0001). High and medium supplementation with vitamin D3 did not affect tumor development (p>0.05).CONCLUSION: In mice, vitamin D levels in the serum, skin, and tumors were augmented by supplementation, but this did not affect the development of UVR-induced skin tumors.
AB - BACKGROUND/AIM: The effect of vitamin D on skin carcinogenesis is unclear. Vitamin D derivatives may protect against ultraviolet radiation (UVR)-induced DNA damage, immune suppression, and skin carcinogenesis. However, some epidemiological studies have reported an increased incidence of skin cancer associated with high serum vitamin D levels. We investigated the effect of vitamin D supplementation on serum, skin, and tumor vitamin D levels and on skin cancer development in hairless immunocompetent mice.MATERIALS AND METHODS: Female C3.Cg-Hrhr/TifBomTac immunocompetent mice (n=125) were randomly separated into five groups. Two groups received a high vitamin D3 diet (4.5 μg/day/mouse). One group received a medium vitamin D3 diet (2.3 μg/day/mouse). Two groups received a standard diet (0.045 μg/day/mouse). Three standard erythema doses of UVR were given three times per week to three groups.RESULTS: Animals on a high vitamin D3 diet had ~150-fold higher serum vitamin D3 levels (p=0.00016) and 3-fold higher serum 25-hydroxyvitamin D3 [25(OH)D3] levels (p=0.00016) than those on a standard diet. For mice on the medium vitamin D3 diet, serum vitamin D3 and 25(OH)D3 levels were 18-fold and 2.3-fold higher than for the standard diet, respectively (p=0.00016). All UVR-exposed mice developed tumors. Vitamin D3 levels were lower in the tumor than the skin (p<0.0001). High and medium supplementation with vitamin D3 did not affect tumor development (p>0.05).CONCLUSION: In mice, vitamin D levels in the serum, skin, and tumors were augmented by supplementation, but this did not affect the development of UVR-induced skin tumors.
KW - Animals
KW - Carcinogenesis
KW - Carcinoma, Squamous Cell/complications
KW - Cholecalciferol/pharmacology
KW - Female
KW - Mice
KW - Neoplasms, Radiation-Induced/etiology
KW - Skin Neoplasms/complications
KW - Ultraviolet Rays/adverse effects
KW - Vitamin D/pharmacology
KW - Vitamins/pharmacology
UR - http://www.scopus.com/inward/record.url?scp=85139124345&partnerID=8YFLogxK
U2 - 10.21873/anticanres.16017
DO - 10.21873/anticanres.16017
M3 - Journal article
C2 - 36192014
SN - 0250-7005
VL - 42
SP - 5083
EP - 5090
JO - Anticancer Research
JF - Anticancer Research
IS - 10
ER -