Photomutagenicity of Retinyl Palmitate by Ultraviolet A Irradiation in Mouse Lymphoma Cells

摘要

Retinyl palmitate (RP), a storage form of vitamin A, is frequently used as a cosmetic ingredient, with more than 700 RP-containing cosmetic products on the U.S. market in 2004. There are concerns for the possible genotoxicity and carcinogenicity of RP when it is exposed to sunlight. To evaluate the photomutagenicity of RP in cells when exposed to ultraviolet A (UVA) light, L5178Y/Tk^+/− mouse lymphoma cells were treated with different doses of RP alone/or in the presence of UVA light. Treatment of the cells with RP alone at the dose range of 25–100 μmg/ml did not increase mutant frequencies (MFs) over the negative control, whereas treatment of cells with 1–25 μg/ml RP under UVA light (82.8 mJ/cm²/min for 30 min) produced a dose-dependent mutation induction. The mean induced MF (392 × 10⁻⁶) for treatment with 25 mg/ml RP under UVA exposure was about threefold higher than that for UVA alone (122 × 10⁻⁶), a synergistic effect. To elucidate the underlying mechanism of action, we examined the mutants for loss of heterozygosity (LOH) at four microsatellite loci spanning the entire chromosome 11, on which the Tk gene is located. The mutational spectrum for the RP + UVA treatment was significantly different from the negative control, but not significantly different from UVA exposure alone. Ninety four percent of the mutants from RP + UVA treatment lost the Tk⁺ allele, and 91% of the deleted sequences extended more than 6 cM in chromosome length, indicating clastogenic events affecting a large segment of the chromosome. These results suggest that RP is photomutagenic in combination with UVA exposure in mouse lymphoma cells, with a clastogenic mode-of-action.