Protective effects of selenocystine against γ-radiation-induced genotoxicity in Swiss albino mice.
Selenocystine (CysSeSeCys), a diselenide aminoacid exhibiting glutathione peroxidase-like activity and selective antitumor effects, was examined for in vivo antigenotoxic and antioxidant activity in Swiss albino mice after exposure to a sublethal dose (5 Gy) of γ-radiation. For this, CysSeSeCys was administered intraperitoneally (i.p.) to mice at a dosage of 0.5 mg/kg body weight for 5 consecutive days prior to whole-body γ-irradiation. When examined in the hepatic tissue, CysSeSeCys administration reduced the DNA damage at 30 min after radiation exposure by increasing the rate of DNA repair. Since antigenotoxic agents could alter the expression of genes involved in cell cycle arrest and DNA repair, the transcriptional changes in p53, p21 and GADD45α were monitored in the hepatic tissue by real-time PCR. The results show that CysSeSeCys alone causes moderate induction of these three genes. However, CysSeSeCys pretreatment resulted in a suppression of radiation-induced enhancement of p21 and GADD45α expression, but did not affect p53 expression. Further analysis of radiation-induced oxidative stress markers in the same tissue indicated that CysSeSeCys significantly inhibits lipid peroxidation and prevents the depletion of antioxidant enzymes and glutathione (GSH) levels. Additionally, it also prevents radiation-induced DNA damage in other radiation sensitive cellular systems like peripheral leukocytes and bone marrow, which was evident by a decrease in comet parameters and micronucleated polychromatic erythrocytes (mn-PCEs) frequency, respectively. Based on these observations, it is concluded that CysSeSeCys exhibits antigenotoxic effects, reduces radiation-induced oxidative stress, and is a promising candidate for future exploration as a radioprotector.
Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India. kamit@barc.gov.in
Amit
A
Kunwar
S
S
Jayakumar
H N
HN
Bhilwade
P P
PP
Bag
H
H
Bhatt
R C
RC
Chaubey
K I
KI
Priyadarsini
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D003553:Cystine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays / Q000009:adverse effects*; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D005979:Glutathione Peroxidase / Q000378:metabolism / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D015162:Micronucleus Tests / Q000379:methods; D009152:Mutagenicity Tests / Q000379:methods; D009687:Nuclear Proteins / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D016566:Organoselenium Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects*; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D014916:Whole-Body Irradiation / Q000379:methods; D000097642:GADD45 Proteins
D000975:Antioxidants; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D003553:Cystine; D005978:Glutathione; D005979:Glutathione Peroxidase; D009687:Nuclear Proteins; D016566:Organoselenium Compounds; D011837:Radiation-Protective Agents; D016159:Tumor Suppressor Protein p53; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C009226:selenocystine
Oncogene. 1996 Nov 21;13(10):2255-63
8950993
Int J Biochem Cell Biol. 2009 Mar;41(3):666-76
18718551
Mutat Res. 2008 Jul 31;654(2):145-9
18582598
Int J Radiat Biol. 2005 Aug;81(8):567-79
16298938
DNA Repair (Amst). 2008 Nov 1;7(11):1835-45
18703169
Mutat Res. 2007 Jul 10;631(1):44-54
17507284
Cancer Biol Ther. 2006 May;5(5):529-35
16627976
Nature. 2003 Aug 14;424(6950):741; discussion 742
12917673
Cell Mol Life Sci. 2000 Dec;57(13-14):1864-73
11215513
Toxicol Appl Pharmacol. 2006 Jul 15;214(2):136-43
16442139
Med Phys. 1982 May-Jun;9(3):311-23
6810077
Curr Med Chem Anticancer Agents. 2005 Nov;5(6):637-52
16305485
Pharmacol Res. 2002 Jun;45(6):447-54
12162944
Evid Based Complement Alternat Med. 2005 Dec;2(4):529-36
16322811
Nucleic Acids Res. 2002 May 1;30(9):e36
11972351
Med Hypotheses. 2006;67(2):318-22
16574336
JAMA. 1996 Dec 25;276(24):1957-63
8971064
Mutat Res. 2001 Apr 18;475(1-2):123-39
11295158
Biochem Pharmacol. 2008 Feb 1;75(3):773-80
18028880
Anal Biochem. 1976 Jul;74(1):214-26
962076
Cancer Lett. 1981 Jun;13(1):7-14
7030471
J Agric Food Chem. 2008 Nov 26;56(22):10574-81
18959417
Mol Cell Biol. 2000 May;20(10):3705-14
10779360
Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14548-53
12357032
Biomed Pharmacother. 2003 May-Jun;57(3-4):134-44
12818475
Curr Med Chem. 2004 Jun;11(12):1657-69
15180570
Mutat Res. 1996 Sep 23;356(2):147-54
8841479
Biomed Pharmacother. 2009 Feb;63(2):105-13
18511231
Mutat Res. 2005 Dec 11;591(1-2):224-36
16099479
Mutat Res. 2008 Jun 30;654(1):1-7
18436471
Int J Radiat Biol. 2008 Apr;84(4):285-98
18386194
J Phys Chem B. 2008 Apr 10;112(14):4441-6
18341323
Int J Cancer. 2007 Apr 1;120(7):1410-7
17205524
Mutat Res. 1991 Sep-Oct;250(1-2):73-7
1719391
J Cell Biochem. 2007 Dec 1;102(5):1214-24
17471506
Int J Radiat Biol. 1994 Jan;65(1):27-33
7905906
Free Radic Biol Med. 2010 Feb 1;48(3):399-410
19931386
Cancer Res. 1986 Jul;46(7):3384-8
2423232
J Inorg Biochem. 2008 Jan;102(1):110-8
17804075
Biol Trace Elem Res. 2011 May;140(2):127-38
20424929
Mutat Res. 2004 Dec 2;568(1):5-20
15530535
Arch Toxicol. 2010 Dec;84(12):919-38
20871980
Mutat Res. 2004 Jul 13;551(1-2):181-97
15225592
Chem Biol Interact. 2007 Jan 5;165(1):22-32
17113058
Mutat Res. 2002 Aug 26;519(1-2):37-48
12160890
Naunyn Schmiedebergs Arch Pharmacol. 2010 Jul;382(1):89-101
20508917
Mutat Res. 2004 May 9;560(1):19-26
15099820
Radiat Environ Biophys. 2009 Nov;48(4):379-84
19756688
Carcinogenesis. 1989 May;10(5):823-6
2539914
Nature. 1993 Dec 16;366(6456):701-4
8259214