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Toxicol Lett. 2015 Dec 15;239(3):182-93. doi: 10.1016/j.toxlet.2015.09.024. Epub 2015 Oct 9.

Benzophenone 1 induced photogenotoxicity and apoptosis via release of cytochrome c and Smac/DIABLO at environmental UV radiation.

Author information

1
Photobiology Division, CSIR-Indian Institute of Toxicology Research, P.O. Box 80, M.G. Marg, Lucknow 226001, India; Academy of Scientific and Innovative Research, CSIR-IITR Campus, Lucknow, India.
2
Photobiology Division, CSIR-Indian Institute of Toxicology Research, P.O. Box 80, M.G. Marg, Lucknow 226001, India.
3
Transmission Electron Microscopy Laboratory, CSIR-IITR, Lucknow, India.
4
Developmental Toxicology, CSIR-Indian Institute of Toxicology Research, P.O. Box 80, M.G. Marg, Lucknow 226001, India.
5
Photobiology Division, CSIR-Indian Institute of Toxicology Research, P.O. Box 80, M.G. Marg, Lucknow 226001, India. Electronic address: ratanray.2011@rediffmail.com.

Abstract

Solar UV radiation is main factor of photocarcinogenesis, photoageing, and phototoxicity; thus, protection from UV radiation is major concern. Sunscreens containing UV filters are suggested as sun safe practices, but safety of UV filters remains in controversies. Benzophenone-1 (BP1) is commonly used in sunscreens as UV blocker. We assessed the photogenotoxicity and apoptotic parameters in human keratinocytes (HaCaT cells) by western blot, immunocytochemistry, flowcytometry, comet assay and TEM imaging. Our results exposed that BP1 photosensitized and generated intracellular ROS (2.02 folds) under sunlight/UVR. Decrease in cell viability was recorded as 80.06%, 60.98% and 56.24% under sunlight, UVA and UVB, respectively. Genotoxic potential of BP1 was confirmed through photomicronuclei and CPDs formation. BP1 enhanced lipid peroxidation and leakage of LDH enzyme (61.7%). Apoptotic cells were detected by AnnexinV/PI staining and sub G1 population of cell cycle. BP1 induced up regulation of apoptotic proteins Bax/Bcl2 ratio, Apaf-1, cytochrome c, Smac/DIABLO and cleaved caspase 3 was noticed. Down regulation of pro caspase 3 was inhibited by Z-VAD-fmk (inhibitor of caspase). Thus, study established the involvement of BP1 in photogenotoxicity and apoptosis via release of cytochrome c and Smac/DIABLO. These findings suggest sunscreen user to avoid BP1 in cosmetics preparation for its topical application.

KEYWORDS:

Caspase 3; Cytochrome c; DNA damage; Photomicronuclei; Phototoxicity; Smac/DIABLO

PMID:
26440554
DOI:
10.1016/j.toxlet.2015.09.024
[Indexed for MEDLINE]

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