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ToxSci Advance Access published online on August 17, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi291
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Published by Oxford University Press 2005.
Received May 24, 2005
Accepted June 27, 2005

Genetic Toxicology

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

Nan Mei 1, Qingsu Xia 2, Ling Chen 3, Martha M. Moore 1, Peter P. Fu 2*, and Tao Chen 1

1 Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079, USA
2 Division of Biochemical Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079, USA
3 Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079, USA; Current address: College of Life Science and Technology, Shanghai Jiao Tong University, Shanghai, China

* To whom correspondence should be addressed.
Peter P. Fu, E-mail: pfu{at}nctr.fda.gov


  Abstract

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 µg/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 dosedependent mutation induction. The mean induced MF (392 x 10-6) for treatment with 25 µg/ml RP under UVA exposure was about 3-fold higher than that for UVA alone (122 x 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.

Keywords: Retinyl palmitate; UVA; mouse lymphoma assay; photomutagenicity; loss of heterozygosity; mutant frequency.
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J Yan, Q Xia, W. Wamer, M. Boudreau, A Warbritton, P. Howard, and P. Fu
Levels of retinyl palmitate and retinol in the skin of SKH-1 mice topically treated with retinyl palmitate and concomitant exposure to simulated solar light for thirteen weeks.
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[Abstract] [PDF]


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