RESUMO
Fragrances are used in almost every cosmetic product. International Fragrance Association (IFRA) is the regulatory body that controls the use of fragrances in cosmetic products. Methyl-N-methylanthranilate (DMA) is a naturally derived fragrance, commonly used in cosmetic products such as fine perfumes, skin care products, etc. But there is a lack of detailed study in terms of its phototoxic and photogenotoxicity mechanisms under UVA/sunlight exposure. In this study, we have shown that DMA photodegrades in 4 h under UVA (1.5 mW/cm2) and sunlight. DMA (0.0001%-0.0025%) significantly reduced the cell viability as demonstrated by NRU and MTT assays in a dose-dependent manner under UVA (5.4 J/cm2) and sunlight (1 h) exposure in the HaCaT cell line. It generated excessive intracellular ROS (superoxide anion radical via type-I photodynamic reaction), resulting in lysosomal destabilization and mitochondrial membrane depolarization. Photo-activated DMA caused DNA fragmentation as observed by olive tail moment. DNA double-strand breaks was demonstrated by phosphorylation of H2AX-histone protein and formation of photo-micronuclei in skin keratinocytes. Additionally, photo-activated DMA upregulated the oxidative stress marker gene hemeoxygenase-1 and apoptotic marker genes (cytochrome-C, caspase-3, caspase-9). Activated caspase-cascade pathway established that photo-activated DMA can potentially trigger apoptosis in the human skin cells.