Mujtaba Syed Faiz, Dwivedi Ashish, Yadav Neera, Ch Ratnasekhar, Kushwaha Hari Narayan, Mudiam Mohana K R, Singh Gajendra, Ray Ratan S
Photobiology Division, CSIR - Indian Institute of Toxicology Research, India; College of Pharmacy, Faculty of Pharmaceutical Sciences, Pt. B.D.S University of Health Sciences, Rohtak, Haryana, India.
Photobiology Division, CSIR - Indian Institute of Toxicology Research, India.
J Photochem Photobiol B. 2015 Jan;142:92-102. doi: 10.1016/j.jphotobiol.2014.11.006. Epub 2014 Dec 2.
Benz(a)anthracene (BA) is an ubiquitous environmental pollutant of polycyclic aromatic hydrocarbon's (PAHs) family. We showed superoxide (O2(-)) catalyzed BA photo modification and apoptosis in HaCaT keratinocytes under sunlight exposure. O2(-) generation was confirmed by quenching through superoxide dismutase (SOD). BA induced photocytotoxicity were investigated through MTT and NRU assay. We proposed DNA insults such as single and double strand breakage and CPDs formation which results in cell cycle arrest and apoptosis by photosensitized BA. BA induced apoptosis was caspase dependent and occurred through a mitochondrial pathway. Reduction of mitochondrial membrane potential, translocation of Bax to mitochondria and cytochrome c release favors involvement of mitochondria in BA phototoxicity. AO/EB double staining and TEM analysis also support apoptotic cell death. We propose a p21 regulated apoptosis via expression of Bax, and cleaved PARP under sunlight exposure. Thus, we conclude that it is imperative to avoid solar radiation during peak hr (between 11A.M. and 3P.M.) when the amount of solar radiation is high, in the light of DNA damage which may lead to mutation or skin cancer through photosensitized BA under sunlight exposure. Concomitantly, investigation is urgently required for the photosafety of BA photoproducts reaching in the environment through photomodification.
苯并(a)蒽（BA）是多环芳烃（PAHs）家族中一种普遍存在的环境污染物。我们发现，在阳光照射下，超氧阴离子（O2(-)）可催化BA在HaCaT角质形成细胞中的光修饰作用并诱导细胞凋亡。通过超氧化物歧化酶（SOD）淬灭法证实了O2(-)的产生。通过MTT和NRU试验研究了BA诱导的光细胞毒性。我们提出，DNA损伤如单链和双链断裂以及环丁烷嘧啶二聚体（CPD）的形成，会导致细胞周期停滞和由光致敏BA引起的细胞凋亡。BA诱导的细胞凋亡依赖于半胱天冬酶，并且通过线粒体途径发生。线粒体膜电位的降低、Bax向线粒体的转位以及细胞色素c的释放有利于线粒体参与BA的光毒性作用。AO/EB双重染色和透射电镜分析也支持凋亡性细胞死亡。我们提出，在阳光照射下，p21通过Bax的表达和PARP的裂解来调节细胞凋亡。因此，鉴于在阳光照射下，DNA损伤可能通过光致敏BA导致突变或皮肤癌，我们得出结论，在太阳辐射量高的高峰时段（上午11点至下午3点之间）避免太阳辐射至关重要。与此同时，迫切需要对通过光修饰进入环境的BA光产物的光安全性进行研究。
