Furocoumarins potentiate UVA-induced DNA damage in skin melanocytes

Abstract

Epidemiological studies have found that high citrus fruit consumption was associated with higher risk of skin cancer. Citrus fruits and some vegetables contain furocoumarins, which may interact with ultraviolet radiation to induce skin cancer. We aimed to determine the effects of two furocoumarins, including 8-methoxypsoralen (8-MOP) and 6′,7′-dihydroxybergamottin (DHB), on UVA-induced DNA damage in human epidermal melanocytes, the origin of melanoma. Our hypothesis was that these dietary furocoumarins increase UVA-induced DNA damage in melanocytes, compared to cells exposed to UV alone. We incubated melanocytes with 8-MOP or DHB, followed by exposure to physiological doses of UVA radiation. We used Western blots to quantify the UVA-induced DNA damage measured by the fraction of phosphorylated histone variant H2AX (γH2AX), which is a marker of DNA damage, relative to total H2AX (γH2AX/H2AX) in the presence or absence of furocoumarins. To quantify the UVA-induced change in γH2AX/H2AX, we calculated the UVA:Control ratio as the ratio of γH2AX/H2AX in UVA-exposed cells to that in cells without UVA (control). The mean UVA:Control ratios were borderline significantly higher for cells treated with 8-MOP and significantly higher for cells treated with DHB, compared to that of untreated cells. This study suggests that furocoumarins (particularly 8-MOP and DHB) enhance UVA-induced DNA damage in melanocytes, which is a potential novel mechanism for citrus and furocoumarins to elevate the risk of skin cancer.