Radioprotective effect of sulfasalazine on mouse bone marrow chromosomes

• Published in: Mutagenesis 2008-07, Vol.23 (4), p.285-292
• Main Authors: Mantena, Sudheer K., Unnikrishnan, M. K., Uma Devi, P.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Bone Marrow Cells - radiation effects; Chromosomes - drug effects; Chromosomes - metabolism; Chromosomes - radiation effects; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Female; Fundamental and applied biological sciences. Psychology; Gamma Rays; Male; Mice; Molecular and cellular biology; Molecular genetics; Mutagenesis. Repair; Radiation-Protective Agents - adverse effects; Radiation-Protective Agents - pharmacology; Sulfasalazine - adverse effects; Sulfasalazine - pharmacology; Time Factors
• ISSN: 0267-8357; 1464-3804
• DOI: 10.1093/mutage/gen005

Sulfasalazine (SAZ), a prescribed drug for inflammatory bowel disease, is a potent scavenger of reactive oxygen species. The present study was undertaken to ascertain its ability to protect against gamma radiation-induced damage. Acute toxicity of the drug was studied taking 24-h, 72-h and 30-day mortality after a single intraperitoneal injection of 400–1200 mg/kg body weight (b.wt.) of the drug. The drug LD50 for 24- and 72-h/30-day survival were found to be 933 and 676 mg/kg b.wt., respectively. The optimum time of drug administration and drug dose-dependent effect on in vivo radiation protection of bone marrow chromosomes was studied in mice. Injection of 30–180 mg/kg SAZ 30 min before gamma irradiation (RT) with 4 Gy produced a significant dose-dependent reduction in the RT-induced percent aberrant metaphases and in the frequency of micronucleated erythrocytes at 24 h after exposure, with a corresponding decrease in the different types of aberrations. The optimum dose for protection without drug toxicity was 120 mg/kg b.wt. At this dose, SAZ produced >60% reduction in the RT-induced percent aberrant metaphases and micronucleated erythrocytes. SAZ also produced a significant increase in the ratio of polychromatic erythrocytes to normochromatic erythrocytes from that of irradiated control. Injection of 120 mg/kg of the drug 60 or 30 min before or within 15 min after 4 Gy whole-body RT resulted in a significant decrease in the percent of aberrant metaphases and in the frequency of micronucleated erythrocytes at 24 h post-irradiation; the maximum effect was seen when the drug was administered 30 min before irradiation. These results show that SAZ protect mice against RT-induced chromosomal damage and cell cycle progression delay. SAZ also protected plasmid DNA (pGEM-7Zf) against Fenton's reactant-induced breaks, suggesting free radical scavenging as one of the possible mechanism for radiation protection.