# Role of Vitamin D in cutaneous DNA repair

> **NIH VA I01** · VETERANS AFFAIRS MED CTR SAN FRANCISCO · 2020 · —

## Abstract

Both vitamin D deficiency and skin cancers arising from epidermal keratinocytes are highly prevalent in
Veterans. Although exposure to the ultraviolet (UV) wavelengths normally found in sunlight initiates vitamin D
biosynthesis, the practice is not currently recommended since UV is also the principal cause of skin cancers.
However, there remains uncertainty as to whether the relatively low doses sufficient for vitamin D production in
the skin are associated with a meaningful risk of skin cancer in healthy individuals, and the Institute of
Medicine's report on this topic identified resolving this issue as a major research need. Based on work in both
our laboratory and those of others, there is evidence that UV-inducible mechanisms such as DNA repair might
be directly coupled to vitamin D signaling. For example, we have observed that mice lacking the vitamin D
receptor are prone to develop UV-induced epidermal tumors, and vitamin D and some of its metabolites induce
DNA repair proteins. On the other hand, mice unable to synthesize the most biologically active form of vitamin
D are not tumor-prone. However, it remains possible that one or more of the multiple other vitamin D
metabolites does have anti-photocarcinogenic effects, including induction of nucleotide excision repair activity,
the principal mechanism for removing UV-induced DNA lesions. The overall hypothesis of this research
proposal is that vitamin D or its derivatives stimulate compensatory mechanisms to repair the collateral DNA
damage associated with its own UV-mediated photosynthesis and thus minimizes photocarcinogenic effects.
In Aim I, cultured keratinocytes and epidermal explants derived from CYP27B1-null mice will be used to
compare the activities of major vitamin D3 metabolites for their effects on nucleotide excision repair. Both
exogenous supplementation and chemical inhibition to modulate endogenous vitamin D metabolite levels will
be employed, and expression of repair genes as well as repair activity and UV resistance will be assayed. In
Aim II, both genomic and non-genomic mechanisms for vitamin D's effects on DNA repair will be investigated.
Cultured keratinocytes and mouse epidermal explants will be used to assess the relevance of the vitamin D
receptor in DNA repair, and the assembly and stability of nucleotide excision repair factors at lesions. Aim III
will use mice treated with the most active vitamin D derivative and the broad cytochrome P450 inhibitor,
ketoconazole, to assess whether supplementation or depletion of the major vitamin D3 metabolites protects
animals from photocarcinogenesis, or predisposes them to it. Mutational spectra of tumors in the TP53 and
XPC genes will also be analyzed to understand the pathways involved. These studies should make an
important contribution to understanding the physiological and cellular mechanistic role of vitamin D in
regulating DNA repair in skin and in suppressing UV photocarcinogenesis. The resulting fundamental biologica...

## Key facts

- **NIH application ID:** 9815328
- **Project number:** 5I01BX003224-04
- **Recipient organization:** VETERANS AFFAIRS MED CTR SAN FRANCISCO
- **Principal Investigator:** DENNIS H OH
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2016-10-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9815328

## Citation

> US National Institutes of Health, RePORTER application 9815328, Role of Vitamin D in cutaneous DNA repair (5I01BX003224-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9815328. Licensed CC0.

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