Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 63-79 |
| Number of pages | 17 |
| Journal | Mutation Research - Genetic Toxicology and Environmental Mutagenesis |
| Volume | 650 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2008 |
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In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis, Vol. 650, No. 1, 2008, p. 63-79.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - In vivo radioprotection by 5-aminosalicylic acid
AU - Mantena, S.K.
AU - Unnikrishnan, M.K.
AU - Joshi, R.
AU - Radha, V.
AU - Devi, P.U.
AU - Mukherjee, T.
N1 - Cited By :17 Export Date: 10 November 2017 CODEN: MRGMF Correspondence Address: Mantena, S.K.; Department of Pharmacology, College of Pharmaceutical Sciences, Manipal, 576119, India; email: sushdheer@yahoo.com Chemicals/CAS: mesalazine, 89-57-6; protein p21, 85306-28-1; Mesalamine, 89-57-6; Radiation-Protective Agents; Tumor Suppressor Protein p53 Manufacturers: Sigma, United Kingdom References: Barcellos-Hoff, M.H., Park, C., Wright, E.G., Radiation and the microenvironment-tumorigenesis and therapy (2005) Nat. Rev.-Cancer, 58, pp. 867-875; Sonntag, V.C., (1987) The Chemical Basis of Radiation Biology, , Taylor and Francis, London; Weiss, J.F., Kumar, K.S., Antioxidant mechanisms in radiation injury and radioprotection (1988) Cellular Antioxidant Defence Mechanisms, pp. 163-189. , Chow C.K. (Ed), CRC Press, Florida; Monig, H., Messerschmidt, O., Streffer, C., (1990) Chemical radioprotection in mammals and in man. 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PY - 2008
Y1 - 2008
N2 - The radioprotective effect of 5-aminosalicylic acid (5ASA) was investigated in mouse bone marrow. The present study was aimed at investigating the radioprotective effect of pre-irradiation treatment with 5ASA against a range of whole-body lethal (8-11 Gy) and sublethal (1-4 Gy) doses of gamma-radiation (RT) in adult Swiss albino mice. Protection against lethal irradiation was evaluated from 30-day mouse survival and against sublethal doses was assessed from chromosomal aberrations in the bone marrow 24 h after irradiation. An intraperitoneal injection of 5ASA at a dose of 25 mg/kg body weight (b. wt.) 30 min before lethal RT increased survival, giving a dose modification factor (DMF) of 1.08. Injection of 5ASA (25 mg/kg b. wt.) 60 or 30 min before or within 15 min after 3 Gy whole body RT resulted in a significant decrease in the radiation-induced aberrant metaphases, at 24 h post-irradiation. Maximum effect was seen when the drug was administered 30 min before irradiation. 5ASA (25 mg/kg b. wt.) significantly reduced the number of aberrant metaphases and the different types of aberrations at all the radiation doses (1-4 Gy) tested, giving a DMFs of 1.43 for number of aberrant metaphases. 5ASA pretreatment also significantly enhanced the endogenous spleen colonies in mouse exposed to 11 Gy RT. Pretreatment with 5ASA, protected plasmid DNA (pGEM-7Zf) against breakage induced by RT and Fenton reactants. Using nanosecond pulse radiolysis technique, the bimolecular rate constant of the reaction of 5ASA with hydroxyl radical was found to be 6.7 × 109 M-1 s-1. The p53 and p21 protein levels of bone marrow and spleen were evaluated to identify the specific molecular mechanisms. Both p53 and p21 increased 24 h after 6 Gy irradiation, while treatment with 5ASA inhibited this RT-induced increase. Therefore, the present data suggest that 5ASA pretreatment decreases death caused by RT-induced gastrointestinal and hemopoeitic syndromes. The proposed mechanism of radioprotection by 5ASA is through the inhibition of damage to DNA, lipids, and proteins; and prevention of RT-induced increased expression of p53 and p21. © 2007 Elsevier B.V. All rights reserved.
AB - The radioprotective effect of 5-aminosalicylic acid (5ASA) was investigated in mouse bone marrow. The present study was aimed at investigating the radioprotective effect of pre-irradiation treatment with 5ASA against a range of whole-body lethal (8-11 Gy) and sublethal (1-4 Gy) doses of gamma-radiation (RT) in adult Swiss albino mice. Protection against lethal irradiation was evaluated from 30-day mouse survival and against sublethal doses was assessed from chromosomal aberrations in the bone marrow 24 h after irradiation. An intraperitoneal injection of 5ASA at a dose of 25 mg/kg body weight (b. wt.) 30 min before lethal RT increased survival, giving a dose modification factor (DMF) of 1.08. Injection of 5ASA (25 mg/kg b. wt.) 60 or 30 min before or within 15 min after 3 Gy whole body RT resulted in a significant decrease in the radiation-induced aberrant metaphases, at 24 h post-irradiation. Maximum effect was seen when the drug was administered 30 min before irradiation. 5ASA (25 mg/kg b. wt.) significantly reduced the number of aberrant metaphases and the different types of aberrations at all the radiation doses (1-4 Gy) tested, giving a DMFs of 1.43 for number of aberrant metaphases. 5ASA pretreatment also significantly enhanced the endogenous spleen colonies in mouse exposed to 11 Gy RT. Pretreatment with 5ASA, protected plasmid DNA (pGEM-7Zf) against breakage induced by RT and Fenton reactants. Using nanosecond pulse radiolysis technique, the bimolecular rate constant of the reaction of 5ASA with hydroxyl radical was found to be 6.7 × 109 M-1 s-1. The p53 and p21 protein levels of bone marrow and spleen were evaluated to identify the specific molecular mechanisms. Both p53 and p21 increased 24 h after 6 Gy irradiation, while treatment with 5ASA inhibited this RT-induced increase. Therefore, the present data suggest that 5ASA pretreatment decreases death caused by RT-induced gastrointestinal and hemopoeitic syndromes. The proposed mechanism of radioprotection by 5ASA is through the inhibition of damage to DNA, lipids, and proteins; and prevention of RT-induced increased expression of p53 and p21. © 2007 Elsevier B.V. All rights reserved.
U2 - 10.1016/j.mrgentox.2007.10.005
DO - 10.1016/j.mrgentox.2007.10.005
M3 - Article
SN - 1383-5718
VL - 650
SP - 63
EP - 79
JO - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
JF - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
IS - 1
ER -