title: Cyto-genotoxicity assessment of potential radioprotector, 3,3'-diselenodipropionic acid (DSePA) in Chinese Hamster Ovary (CHO) cells and human peripheral blood lymphocytes.
abstract: Our previous study showed that 3,3'-diselenodipropionic acid (DSePA), a simple, stable, and water-soluble organoselenium exhibiting glutathione peroxidase (GPx)-like activity offered good radioprotection under in vitro and in vivo conditions. Herein, we investigated the anti-genotoxic effect of DSePA in model cellular systems such as Chinese Hamster Ovary (CHO) cell line and human peripheral lymphocytes after exposure to γ-radiation. The measurements on the induction of γ-H2AX foci and micronuclei frequency in the cell nuclei indicated that pretreatment with DSePA significantly prevented the radiation induced DNA damage or genotoxicity and subsequent cytotoxicity without exerting its own toxicity. The maximum protective effect of DSePA was seen at a pre-treatment concentration of 3 μg/ml. The mechanistic investigations in CHO cells revealed that DSePA pretreatment prevented the radiation induced ROS generation, lipid peroxidation and subsequent apoptosis in these cells. Further, it was seen to augment the mRNA expressions of GPx2 significantly and GPx4 marginally without causing much change in the total GPx activity after radiation exposure. These results suggested the roles of GPx2 and GPx4 in DSePA mediated radioprotection. In conclusion our results confirm the nongenotoxic nature of the DSePA and validate its radioprotective efficacy and mechanisms of action in model cellular systems.
authors.affiliation: Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Mumbai 400085, India.
authors.forename: Rajesh Kumar
authors.initials: RK
authors.lastname: Chaurasia
authors.affiliation: Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Mumbai 400085, India. Electronic address: bsdevi@barc.gov.in.
authors.forename: Sreedevi
authors.initials: S
authors.lastname: Balakrishnan
authors.affiliation: Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Mumbai 400085, India. Electronic address: kamit@barc.gov.in.
authors.forename: Amit
authors.initials: A
authors.lastname: Kunwar
authors.affiliation: Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Mumbai 400085, India.
authors.forename: Usha
authors.initials: U
authors.lastname: Yadav
authors.affiliation: Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Mumbai 400085, India.
authors.forename: Nagesh
authors.initials: N
authors.lastname: Bhat
authors.affiliation: Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Mumbai 400085, India.
authors.forename: Kshiti
authors.initials: K
authors.lastname: Anjaria
authors.affiliation: Department of Studies in Physics, Mangalore University, Mangalagangotri 574199, India.
authors.forename: Rajesha
authors.initials: R
authors.lastname: Nairy
authors.affiliation: Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Mumbai 400085, India.
authors.forename: Balvinder Kaur
authors.initials: BK
authors.lastname: Sapra
authors.affiliation: Chemistry Division, Bhabha Atomic Research Centre, Mumbai 400085, India.
authors.forename: Vimal Kumar
authors.initials: VK
authors.lastname: Jain
authors.affiliation: Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Mumbai 400085, India.
authors.forename: K Indira
authors.initials: KI
authors.lastname: Priyadarsini
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D005786:Gene Expression Regulation / Q000187:drug effects; D006657:Histones / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000528:radiation effects*; D008297:Male; D020714:Maximum Tolerated Dose; D048629:Micronuclei, Chromosome-Defective / Q000528:radiation effects; D011422:Propionates / Q000494:pharmacology* / Q000633:toxicity; D011837:Radiation-Protective Agents / Q000494:pharmacology* / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D018036:Selenium Compounds / Q000494:pharmacology* / Q000633:toxicity
chemical_list: C524945:3,3'-diselenodipropionic acid; D006657:Histones; D011422:Propionates; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D018036:Selenium Compounds
keywords: Cytotoxicity; DSePA; Genotoxicity; Glutathione peroxidase; γ-Radiation