Preventing photogenotoxicity: Stable, broad-spectrum protection critical for sunscreen

Key Points

National report - Results of an in vitro study evaluating sunscreen prevention of UV-induced genotoxic damage indicates that a product's level of UVA absorption has greater relevance than its SPF value.

The methods involved the same experimental set-up used for in vitro SPF testing. Using a solar simulator to mimic realistic UV exposure conditions, cultured human keratinocytes were irradiated for up to 60 minutes, with or without sunscreen protection, provided by spreading a standardized amount of product or placebo on an overlying, UV-transparent slide.

Three commercially available SPF 15 sunscreens were evaluated. Assays performed evaluated cell survival and genotoxic damage using three different endpoints.

The three sunscreens performed comparably in protecting against irradiation-induced cytotoxicity.

However, the assays for genotoxic damage showed one product, which contained Mexoryl SX (L'Oréal), consistently provided significantly greater protection than the other two sunscreens.

Findings from spectroradiometry testing showed the Mexoryl SX product was the only sunscreen formulation that was both photostable and provided broad-spectrum absorption in the UVA and UVB range, according to Laurent Marrot, Ph.D., head of the phototoxicology unit, safety research department, L'Oréal Advanced Research, Aulnay-sous-Bois, France.

"By combining these in vitro biological approaches with spectroradiometric measurements to determine the nature and the intensity of UV transmitted through a calibrated product layer, we are able to attribute the adverse photobiological effects to a precise, inappropriately filtered domain of wavelengths corresponding to UVA radiation," Dr. Marrot says.

Study highlights

"Our study highlights that ... UVA radiation is clearly also involved in sunlight-induced genotoxicity. It is, thus, of importance to provide the public with sunscreens that are efficient and stable over the entire UV radiation range," he tells Dermatology Times.

The Mexoryl SX-containing sunscreen was also formulated with 2 percent avobenzone and 10 percent octocrylene. A second product tested contained 6 percent octinoxate and 3 percent zinc oxide as active ingredients, and the third sunscreen was formulated with 3 percent avobenzone, 2 percent octisalate and 7.5 percent octinoxate.

The spectroradiometry study results showed the Mexoryl SX-containing product absorbed UV from 300 nm to 380 nm and maintained a stable transmission spectrum after 60 minutes of UV exposure. The product with octinoxate and zinc oxide was photostable but did not absorb UVA efficiently, while the third sunscreen provided broad-spectrum UV absorption, but its filtering efficiency decreased after 30 minutes of UV exposure.

The genotoxicity-related endpoints assessed in the study included measurement of oxidative DNA damage using the comet assay, detection of pyrimidine dimers by immunochemistry, and quantification of p53 accumulation by ELISA.

Genotoxicity

"Our strategy to study both DNA damage induction and p53 status is a very informative way to evaluate the intensity of a given photogenotoxic stress and to assess 'genome photoprotection' by sunscreen products," Dr. Marrot says.

He says the photocarcinogenic mechanisms of both UVB and UVA radiation involve induction of pyrimidine dimers. In addition, UVA toxicity occurs through generation of reactive oxygen species that trigger various pathways involved in tumor promotion; p53 plays a critical role in protecting the cell's genome integrity.

"Cells can manage low amounts of DNA damage using their basic repair equipment. When DNA damage reaches a critical level, specific signaling pathways, including p53, can be stimulated to maintain homeostasis. P53 allows DNA repair or triggers apoptosis when DNA alteration has reached an unacceptable level, thereby eliminating cells carrying irreparable genetic damage," Dr. Marrot says.

The researchers also highlighted that their study findings, which indicated that a defect of UVA absorption resulted in significant genotoxicity, underscore the limitation of using the SPF rating as a measure of sunscreen protection.

"The SPF rating is the only regulatory protection factor in the labeling of marketed sunscreen products, but it is based on the prevention of erythema, which mostly reflects protection in the UVB range of the solar spectrum," Dr. Marrot says.