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conferenceseries
.com
Volume 4
Toxicology: Open Access
ISSN: 2476-2067
Toxicology Congress 2018
March 12-14, 2018
March 12-14, 2018 Singapore
14
th
World Congress on
Toxicology and Pharmacology
Superoxide mediated apoptosis in cell organelles by photosensitized 1,2:3,4-dibenzanthracene in
HaCaT cells at ambient UV-B and natural sunlight
Ajeet Kumar Srivastav
1
, Syed Faiz Mujtaba
2
, Jyoti Singh
1
, Deepti Chopra
1
, Divya Dubey
1
, Mohammad Anas
1
, Shikha Agnihotry
2
and Ratan Singh Ray
1
1
Indian Institute of Toxicology Research, India
2
Shia PG College, India
P
olycyclic aromatic hydrocarbons (PAHs) are recognized as environmental pollutants because of their intrinsic chemical
stability, high resistance and toxic property worldwide. 1,2:3,4 dibenzanthracene (DBA) is a PAH, produced by incomplete
combustion of fossil fuels, petroleum discharge. It gets adsorbed on atmospheric particles, mixed into soils, used in tattoo ink
and remains for the longest time in the ecosystem. DBA showed strong absorption maxima (λmax) in UV-B (290-320 nm)
with low absorption under UV-A (320-400 nm). DBA generates the significant amount of ROS such as O
2
.-, .OH via type 1
mechanism.
In silico
study of DBA showed the interaction with aryl hydrocarbon receptor. DBA generates ROS photochemically
and intracellularly which was confirmed by DCF/DHE fluorescence intensity while genotoxicity was assessed through comet
assay, Hoechst staining, micronuclei formation. The generation of CPDs and 6-4 photoproduct formation, confirm the photo-
genotoxic potential of DBA. Mitotracker/DAPI, Mitotracker/DHE, Mitotracker/DCF and JC-1 result showed the significant
increase in mitochondrial permeability pore complex formation which leads to the release of cytochrome-c in cytosol showed
strong evidence for apoptotic cell death by photoirradiation DBA. Cell cycle result showed G2/M phase arrest during cell
division. DBA significantly showed over expression of Bax, Parp, Cyt-c, Bak, Caspase 3, Apaf-1, Cathepsin-B, Lamp-1, AhR,
tBid, Calpain-7, γH2Ax, Keap-1, Caspase-12, Caspase-9 and lower expression of Bcl-2, Bid, Hmox and procaspase-3 protein
expressions and up-regulation of Apaf-1, Cyt-C, Bax, Caspase-3, Calpain-7, Cathepsin-B, Nrf-2, Keap-1, AhR, Cdk-2, Cdk-
4, Cycd1, Cycd2, Cycd3, Cdk6, Cyp1a2 and down regulation of Hmox, Bcl-2 genes. The exact mechanism behind DBA
phototoxicity was involvement of ROS generation via type-1 mechanism, reduction of an antioxidant level and activation of
the apoptotic pathway through mitochondria, nucleus as well as endoplasmic reticulum followed by AhR strongly promotes
apoptotic cell death. The study suggests that after the DBA exposure, sunlight/UV-B exposure may avoid preventing from its
harmful effects.
References
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of intracellular calcium concentration by environmental polycyclic aromatic hydrocarbons in human endothelial HMEC-
1 cells.
Environ. Toxicol.
; doi: 10.1002/tox. 20675.
2. Bastianon C, R Zanoni, G Miolo, S Caffieri and E Reddi (2005) Mitochondria and plasma membrane as targets of UV-A
induced toxicity of neuroleptic drugs fluphenazine, perphenazine and thioridazine.
Int. J. Biochem. Cell Biol.
; 37: 901–908.
3. Kung MH, Yukata K, O'Keefe R J, Zuscik M J (2012) Aryl hydrocarbon receptor-mediated impairment of chondrogenesis
and fracture healing by cigarette smoke and benzo(a)pyrene.
J Cell Physiol.
; 227(3): 1062-70.
4. Rao P S, Kumar S (2015) Polycyclic aromatic hydrocarbons and cytochrome P450 in HIV pathogenesis.
Front Microbiol.
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5. Ali D, Verma A, Mujtaba F, Dwivedi A, Hans R K, Ray R S (2011) UVB-induced apoptosis and DNA damaging potential
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Toxicol Lett.
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Biography
Ajeet Kumar Srivastav has his research interest in the study of molecular mechanism involved in skin disease, phototoxicity/photogenotoxicity and molecular
mechanism involved in skin disease by photosensitive drugs, cosmetics preservatives, hair dyes and PAHs under ambient UV-R/sunlight exposure. Presently, he
is working as a Senior Research Fellow at Photobiology Division, Indian Institute of Toxicology Research, Lucknow, India.
srivastav.ajete8@gmail.comAjeet Kumar Srivastav et al., Toxicol Open Access 2018, Volume 4
DOI: 10.4172/2476-2067-C1-005