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 - Funding Information: This research was supported by the Danish Research Center for Skin Cancer (https://vfhk.org/en), Denmark and the Skin Cancer Innovation Clinical Academic Group (SCIN CAG), Greater Copenhagen Health Science Partners (GCHSP), Copenhagen, Denmark. The work was funded by Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark. C.M.L is funded by a grant from the Lundbeck Foundation (R307-2018-3318), Copenhagen, Denmark.

PY - 2022

Y1 - 2022

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 - 25-hydroxyvitamin D

KW - cholecalciferol

KW - D-vitamin

KW - hairless mice

KW - UVR

KW - Vitamin D

U2 - 10.21873/anticanres.16017

DO - 10.21873/anticanres.16017

M3 - Journal article

C2 - 36192014

AN - SCOPUS:85139124345

VL - 42

SP - 5083

EP - 5090

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 10

ER -