Radioprotective effect of sulfasalazine on mouse bone marrow chromosomes

S.K. Mantena, M.K. Unnikrishnan, P. Uma Devi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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. © The Author 2008. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved.
Original languageEnglish
Pages (from-to)285-292
Number of pages8
JournalMutagenesis
Volume23
Issue number4
DOIs
Publication statusPublished - 2008

Fingerprint

Sulfasalazine
Chromosomes
Bone
Bone Marrow
Erythrocytes
Pharmaceutical Preparations
Metaphase
Radiation Protection
Drug-Related Side Effects and Adverse Reactions
Radiation protection
Irradiation
Body Weight
Toxicity
Injections
Lethal Dose 50
Gamma Rays
Mutagens
Intraperitoneal Injections
Inflammatory Bowel Diseases
Free Radicals

Cite this

Mantena, S. K., Unnikrishnan, M. K., & Uma Devi, P. (2008). Radioprotective effect of sulfasalazine on mouse bone marrow chromosomes. Mutagenesis, 23(4), 285-292. https://doi.org/10.1093/mutage/gen005
Mantena, S.K. ; Unnikrishnan, M.K. ; Uma Devi, P. / Radioprotective effect of sulfasalazine on mouse bone marrow chromosomes. In: Mutagenesis. 2008 ; Vol. 23, No. 4. pp. 285-292.
@article{d0d354c0acc6463b8762d49507c10f5f,
title = "Radioprotective effect of sulfasalazine on mouse bone marrow chromosomes",
abstract = "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. {\circledC} The Author 2008. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved.",
author = "S.K. Mantena and M.K. Unnikrishnan and {Uma Devi}, P.",
note = "Cited By :4 Export Date: 10 November 2017 CODEN: MUTAE Correspondence Address: Unnikrishnan, M. K.; Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal 576 104, Karnataka, India; email: mkunnikrishnan@gmail.com Chemicals/CAS: salazosulfapyridine, 599-79-1; Radiation-Protective Agents; Sulfasalazine, 599-79-1 Manufacturers: Sigma, United States References: Monig, H., Messerschmidt, O., Streffer, C., Chemical radioprotection in mammals and in man (1990) Radiation Exposure and Occupational Risks, pp. 97-143. , Scherer, E, Streffer, C. and Trott, K. R, eds, Springer-Verlag, Berlin, Germany, pp; Uma Devi, P., Normal tissue protection in cancer therapy: Progress and prospects (1998) Acta Oncol, 37, pp. 247-252; Riis, P., Anthonsien, P., Wulff, H.R., Folkenborg, O., Bonnevie, O., Binder, V., The prophylactic effect of salazosulphapyridine in ulcerative colitis during long-term treatment: A double-blind trial on patients asymptomatic for one year (1973) Scand. J. Gastroenterol, 8, pp. 71-74; Svartz, N., Ett nytt sulfonamidpreparat. Forelopande meddelande (1941) Nord. Med, 9, p. 544; Hoult, J.R.S., Pharmacological and biochemical actions of sulphasalazine (1986) Drugs, 32, pp. 18-26; Azad Khan, A.K., Piris, J., Truelove, S.C., An experiment to determine the active therapeutic moiety of sulphasalazine (1977) Lancet, 2, pp. 892-895; Klotz, U., Maier, K., Fischer, C., Heinkel, K., Therapeutic efficacy of sulfasalazine and its metabolites in patients with ulcerative colitis and Crohn's disease (1980) N. Engl. J. Med, 303, pp. 1499-1502; Sutherland, L.R., May, G.R., Shaffer, E.A., Sulfasalazine revisited: A meta-analysis of 5-aminosalicylic acid in the treatment of ulcerative colitis (1993) Ann. Intern. Med, 118, pp. 540-549; Pruzanski, W., Stefanski, E., Vadas, P., Ramamurty, N.S., Inhibition of extracellular release of proinflammatory secretory phospholipase A2 by sulfasalazine (1997) Biochem. Pharmacol, 53, pp. 1901-1907; Carlin, G., Djursater, R., Smedegard, G., Inhibitory effects of sulfasalazine and related compounds on superoxide production by human polymorphonuclear leukocytes (1989) Pharmacol. Toxicol, 65, pp. 121-127; Rhodes, J.M., Bartholomew, T.C., Jewell, D.P., Inhibition of leucocyte motility by drugs used in ulcerative colitis (1981) Gut, 22, pp. 642-647; Rubinstein, A., Das, K.M., Melamed, J., Murphy, R.A., Comparative analysis of systemic immunological parameters in ulcerative colitis and idiopathic proctitis: Effect of sulfasalazine in vivo and in vitro (1978) Clin. Exp. Immunol, 33, pp. 217-224; Sheldon, P.J., Webb, C., Grindulis, K.A., Effect of sulphasalazine and its metabolites on mitogen induced transformation of lymphocytes-clues to its clinical action? (1988) Br. J. Rheumatol, 27, pp. 344-349; Fujiwara, M., Mitsui, K., Yamamoto, I., Inhibition of proliferative responses and interleukin 2 production by salazosulfapyridine and its metabolites (1990) Jpn. J. Pharmacol, 54, pp. 121-132; Gaginella, T.S., Walsh, R.E., Sulfasalazine: Multiplicity of action (1992) Dig. Dis. Sci, 37, pp. 801-812; Gionchetti, P., Guarnieri, C., Campieri, M., Belluzzi, A., Brignola, C., Iannoe, P., Miglioli, M., Barbara, L., Scavenger effects of sulfasalazine, 5-aminosalicylic acid, olsalazine on superoxide radical generation (1991) Dig. Dis. Sci, 36, pp. 174-178; Miyachi, Y., Yoshioka, A., Imamura, S., Niwa, Y., Effect of sulfasalazine and its metabolites on the generation of reactive oxygen species (1987) Gut, 28, pp. 190-195; Pronai, L., Yukinobu, I., Lang, I., Feher, J., The oxygen centered radical scavenging activity of sulfasalazine and its metabolites. A direct protection of bowel (1992) Acta Physiol. Hung, 80, pp. 317-323; Rauch, K., Weilland, H., Behandlung der radiogenen kolitis mit salisilazosulfapyridin (azusulfidine) (1972) Strahlentherapie, 143, pp. 660-663; Kilic, D., Ozenirler, S., Egenhan, I., Dursun, A., Sulfasalazine decreases acute gastrointestinal complications due to pelvic radiotherapy (2001) Ann. Pharmacother, 35, pp. 806-810; Kilic, D., Ozenirler, S., Egenhan, I., Dursun, A., Double-blinded, randomized, placebo-controlled study to evaluate the effectiveness of sulphasalazine in preventing acute gastrointestinal complications due to radiotherapy (2000) Radiother. Oncol, 57, pp. 125-129; Lee, Y.S., Kang, S.K., Kim, T.H., Myong, N.H., Jang, J.J., Species, strain and sex differences in susceptibility to gamma radiation combined with diethylnitrosamine (1998) Anticancer Res, 18, pp. 1105-1109; Calabrese, E.J., Baldwin, L.A., The effects of gamma rays on longevity (2000) Biogerontology, 1, pp. 309-319; Ghosh, M.N., (1984) Fundamentals of Experimental Pharmacology, pp. 153-157. , 2nd edn. Scientific Book Agency, Calcutta, India; Geigy, J. R. (1956) Documents Geigy Scientific Tables. 5th edn. J. Board & Co. Ltd., Basle, UK, pp. 26-48; Uma Devi, P., Bisht, K.S., Vinitha, M., A comparative study of radioprotection by ocimum flavonoids and synthetic aminothiol protectors in the mouse (1998) Br. J. Radiol, 71, pp. 782-784; Savage, J.R.K., Classification and relationships of induced chromosomal structural changes (1976) J. Med. Genet, 12, pp. 103-122; Bender, M.A., Awa, A.A., Brooks, A.L., Evans, H.J., Groer, P.G., Littlefield, L.G., Pereira, C., Wachholz, B.W., Current status of cytogenetic procedures to detect and quantify previous exposures to radiation (1988) Mutat. Res, 196, pp. 103-159; Schmid, W., Chemical mutagen testing on in vivo somatic cells (1973) Agents Actions, 3, pp. 77-85; Schmid, W., The micronucleus test (1979) Mutat. Res, 31, pp. 9-15; Wijewickreme, A.N., Krejpcio, Z., Kitts, D.D., Hydroxyl scavenging activity of glucose, fructose and ribose-lysine model Maillard products (1999) J. Food Sci, 64, pp. 457-461; Cole, R.J., Tylor, N., Cole, J., Arlett, C.F., Short-term tests for transplacentally active carcinogens. I. Micronucleus formation in fetal and maternal mouse erythroblasts (1981) Mutat. Res, 80, pp. 141-157; Jagetia, G.C., Ganapathi, N.G., Treatment of mice with a herbal preparation (Liv. 52) reduces the frequency of radiation-induced chromosome damage in bone marrow (1991) Mutat. Res, 253, pp. 123-126; Jagetia, G.C., Venkatesha, V.A., Reddy, T.K., Naringin, a citrus flavonone, protects against radiation-induced chromosome damage in mouse bone marrow (2003) Mutagenesis, 18, pp. 337-343; Carrano, A.V., Heddle, J.A., The fate of chromosome aberrations (1973) J. Theor. Biol, 38, pp. 289-304; Sasaki, H., Lethal sectoring, genomic instability, and delayed division delay in HeLa S3 cells surviving alpha- or X-irradiation (2004) J. Radiat. Res, 45, pp. 497-508; Fenech, M., Cytokinesis-block micronucleus cytome assay (2007) Nat. Protoc, 2, pp. 1084-1104; Hofer, M., Mazur, L., Pospisil, M., Weiterova, L., Znojil, V., Radioprotective action of extracellular adenosine on bone marrow cells in mice exposed to gamma rays as assayed by the micronucleus test (2000) Radiat. Res, 154, pp. 217-221; Yuhas, J.M., Storer, J.B., Chemoprotection against three modes of radiation death (1969) Int. J. Radiat. Biol, 15, pp. 233-237; Uma Devi, P., Prasanna, P.G.S., Radioprotective effect of combinations of WR-2721 and mercaptopropionylglycine on mouse bone marrow chromosomes (1990) Radiat. Res, 124, pp. 165-170; Gupta, R., Uma Devi, P., Protection of mouse chromosomes against whole-body gamma irradiation by SH-compounds (1986) Br. J. Radiol, 59, pp. 625-627; Thomas, B., Uma Devi, P., Chromosome protection by WR-2721 and MPG-single and combination treatments (1987) Strahlenther Onkol, 163, pp. 807-810; Ganasoundari, A., Uma Devi, P., Rao, B.S.S., Enhancement of bone marrow radioprotection and reduction of WR-2721 toxicity by Ocimum sanctum (1998) Mutat. Res, 397, pp. 303-312; Jagetia, G.C., Aruna, R., The herbal preparation abana protects against radiation-induced micronuclei in mouse bone marrow (1997) Mutat. Res, 393, pp. 157-163; Chaubey, R.C., Bhilwade, H.N., Joshi, B.N., Chauhan, P.S., Studies on the migration of micronucleated erythrocytes from bone marrow to the peripheral blood in irradiated Swiss mice (1993) Int. J. Radiat. Biol, 63, pp. 239-245; Sudheer Kumar, M., Unnikrishnan, M.K., Uma Devi, P., Effect of 5-aminosalicylic acid on radiation-induced micronuclei in mouse bone marrow (2003) Mutat. Res, 527, pp. 7-14; Grzelinska, E., Bartkowiak, A., Bartosz, G., Leyko, W., Effect of •OH scavengers on radiation damage to the erythrocyte membrane (1982) Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med, 41, pp. 473-481; Joshi, R., Kumar, S., Unnikrishnan, M., Mukherjee, T., Free radical scavenging reactions of sulfasalazine, 5-aminosalicylic acid and sulfapyridine: Mechanistic aspects and antioxidant activity (2005) Free Radic. Res, 39, pp. 1163-1172; Bishop, J.B., Witt, K.L., Gulati, D.K., MacGregor, J.T., Evaluation of the mutagenicity of the anti-inflammatory drug salicylazosulfapyridine (SASP) (1990) Mutagenesis, 5, pp. 549-554; Iatropoulos, M.J., Williams, G.M., Abdo, K.M., Kari, F.W., Hart, R.W., Mechanistic studies on genotoxicity and carcinogenicity of salicylazosulfapyridine an anti-inflammatory medicine (1997) Exp. Toxicol. Pathol, 49, pp. 15-28; Uma Devi, P., Nagarathnam, A., Rao, B.S.S., DNA damage and repair (2000) Introduction to Radiation Biology, pp. 52-64. , Churchill Livingstone Pvt. Ltd, New Delhi, India, pp; Sasaki, M.S., Matsubara, S., Free radical scavenging in protection of human lymphocytes against chromosome aberration formation by gamma-ray irradiation (1977) Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med, 32, pp. 439-445; Roots, R., Okada, S., Protection of DNA molecules of cultured mammalian cells from radiation-induced single-strand scissions by various alcohols and SH compounds (1972) Int J. Radiat. Biol. Relat. Stud. Phys. Chem. Med, 21, pp. 329-342; Okada, S., Nakamura, N., Sasaki, K., Radioprotection of intracellular genetic material (1983) Radioprotection and Anticarcinogens, pp. 339-356. , Nygaard, O. F. and Simic, M. G, eds, Academic Press, New York, pp; Shimoi, K., Masuda, S., Shen, B., Furugori, M., Kinae, N., Radiation protection effect of antioxidative plant flavonoids in mice (1996) Mutat. Res, 350, pp. 153-161; Abraham, S.K., Sarma, L., Kesavan, P.C., Protective effects of chlorogenic acid, curcumin and β-carotene against c-radiation-induced in vivo chromosomal damage (1993) Mutat. Res, 303, pp. 109-112; Sarma, L., Kesavan, P.C., Protective effects of vitamin C and E against γ-ray-induced chromosomal damage in mouse (1993) Int. J. Radiat. Biol, 63, pp. 759-764; Umegaki, K., Ikegami, S., Inoue, K., Ichikawa, T., Kobayashi, S., Soeno, N., Tomebachi, K., Beta-carotene prevents X-ray induction of micronuclei in human lymphocytes (1994) Am. J. Clin. Nutr, 59, pp. 409-412; O'Neill, P., Fielden, E.M., Primary free radical processes in DNA (1993) Advances in Radiation Biology, pp. 53-120. , Lett, J. T. and Sinclair, W. K, eds, Academic Press, New York, pp; Uma Devi, P., Ganasoundari, A., Rao, B.S.S., Srinivasan, K.K., In vivo radioprotection by ocimum flavonoids: Survival of mice (1999) Radiat. Res, 151, pp. 74-78; Maisin, J.R., Albert, C., Henry, A., Reduction of short-term radiation lethality by biological response modifiers given alone or in association with other chemical protectors (1993) Radiat. Res, 135, pp. 332-337; Michalowski, A.D., On radiation damage to normal tissue and treatment (1994) Acta Oncol, 33, pp. 139-157; Satyamitra, M., Uma Devi, P., Murase, H., Kagiya, V.T., In vivo postirradiation protection by a vitamin E analog, alpha-TMG (2003) Radiat. Res, 160, pp. 655-661; Farooqi, Z., Kesavan, P.C., Radioprotection by caffeine pre- and post-treatment in the bone marrow chromosomes of mice given whole-body c-irradiation (1992) Mutat. Res, 269, pp. 225-230; Gout, P.W., Buckley, A.R., Simms, C.R., Bruchovsky, N., Sulfasalazine, a potent suppressor of lymphoma growth by inhibition of the x(c)-cystine transporter: A new action for an old drug (2001) Leukemia, 15, pp. 1633-1640; Chung, W.J., Lyons, S.A., Nelson, G.M., Hamza, H., Gladson, C.L., Gillespie, G.Y., Sontheimer, H., Inhibition of cystine uptake disrupts the growth of primary brain tumors (2005) J. Neurosci, 25, pp. 7101-7110; Doxsee, D.W., Gout, P.W., Kurita, T., Sulfasalazine-induced cystine starvation: Potential use for prostate cancer therapy (2007) Prostate, 67, pp. 162-171; Fischer-Nielsen, A., Poulsen, H.E., Loft, S., 8-Hydroxydeoxyguanosine in vitro: Effects of glutathione, ascorbate and 5-aminosalicylic acid (1992) Free Radic. Biol. Med, 13, pp. 121-126",
year = "2008",
doi = "10.1093/mutage/gen005",
language = "English",
volume = "23",
pages = "285--292",
journal = "Mutagenesis",
issn = "0267-8357",
publisher = "Oxford University Press",
number = "4",

}

Mantena, SK, Unnikrishnan, MK & Uma Devi, P 2008, 'Radioprotective effect of sulfasalazine on mouse bone marrow chromosomes', Mutagenesis, vol. 23, no. 4, pp. 285-292. https://doi.org/10.1093/mutage/gen005

Radioprotective effect of sulfasalazine on mouse bone marrow chromosomes. / Mantena, S.K.; Unnikrishnan, M.K.; Uma Devi, P.

In: Mutagenesis, Vol. 23, No. 4, 2008, p. 285-292.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Radioprotective effect of sulfasalazine on mouse bone marrow chromosomes

AU - Mantena, S.K.

AU - Unnikrishnan, M.K.

AU - Uma Devi, P.

N1 - Cited By :4 Export Date: 10 November 2017 CODEN: MUTAE Correspondence Address: Unnikrishnan, M. K.; Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal 576 104, Karnataka, India; email: mkunnikrishnan@gmail.com Chemicals/CAS: salazosulfapyridine, 599-79-1; Radiation-Protective Agents; Sulfasalazine, 599-79-1 Manufacturers: Sigma, United States References: Monig, H., Messerschmidt, O., Streffer, C., Chemical radioprotection in mammals and in man (1990) Radiation Exposure and Occupational Risks, pp. 97-143. , Scherer, E, Streffer, C. and Trott, K. R, eds, Springer-Verlag, Berlin, Germany, pp; Uma Devi, P., Normal tissue protection in cancer therapy: Progress and prospects (1998) Acta Oncol, 37, pp. 247-252; Riis, P., Anthonsien, P., Wulff, H.R., Folkenborg, O., Bonnevie, O., Binder, V., The prophylactic effect of salazosulphapyridine in ulcerative colitis during long-term treatment: A double-blind trial on patients asymptomatic for one year (1973) Scand. J. Gastroenterol, 8, pp. 71-74; Svartz, N., Ett nytt sulfonamidpreparat. Forelopande meddelande (1941) Nord. Med, 9, p. 544; Hoult, J.R.S., Pharmacological and biochemical actions of sulphasalazine (1986) Drugs, 32, pp. 18-26; Azad Khan, A.K., Piris, J., Truelove, S.C., An experiment to determine the active therapeutic moiety of sulphasalazine (1977) Lancet, 2, pp. 892-895; Klotz, U., Maier, K., Fischer, C., Heinkel, K., Therapeutic efficacy of sulfasalazine and its metabolites in patients with ulcerative colitis and Crohn's disease (1980) N. Engl. J. Med, 303, pp. 1499-1502; Sutherland, L.R., May, G.R., Shaffer, E.A., Sulfasalazine revisited: A meta-analysis of 5-aminosalicylic acid in the treatment of ulcerative colitis (1993) Ann. Intern. Med, 118, pp. 540-549; Pruzanski, W., Stefanski, E., Vadas, P., Ramamurty, N.S., Inhibition of extracellular release of proinflammatory secretory phospholipase A2 by sulfasalazine (1997) Biochem. Pharmacol, 53, pp. 1901-1907; Carlin, G., Djursater, R., Smedegard, G., Inhibitory effects of sulfasalazine and related compounds on superoxide production by human polymorphonuclear leukocytes (1989) Pharmacol. Toxicol, 65, pp. 121-127; Rhodes, J.M., Bartholomew, T.C., Jewell, D.P., Inhibition of leucocyte motility by drugs used in ulcerative colitis (1981) Gut, 22, pp. 642-647; Rubinstein, A., Das, K.M., Melamed, J., Murphy, R.A., Comparative analysis of systemic immunological parameters in ulcerative colitis and idiopathic proctitis: Effect of sulfasalazine in vivo and in vitro (1978) Clin. Exp. Immunol, 33, pp. 217-224; Sheldon, P.J., Webb, C., Grindulis, K.A., Effect of sulphasalazine and its metabolites on mitogen induced transformation of lymphocytes-clues to its clinical action? (1988) Br. J. Rheumatol, 27, pp. 344-349; Fujiwara, M., Mitsui, K., Yamamoto, I., Inhibition of proliferative responses and interleukin 2 production by salazosulfapyridine and its metabolites (1990) Jpn. J. Pharmacol, 54, pp. 121-132; Gaginella, T.S., Walsh, R.E., Sulfasalazine: Multiplicity of action (1992) Dig. Dis. Sci, 37, pp. 801-812; Gionchetti, P., Guarnieri, C., Campieri, M., Belluzzi, A., Brignola, C., Iannoe, P., Miglioli, M., Barbara, L., Scavenger effects of sulfasalazine, 5-aminosalicylic acid, olsalazine on superoxide radical generation (1991) Dig. Dis. Sci, 36, pp. 174-178; Miyachi, Y., Yoshioka, A., Imamura, S., Niwa, Y., Effect of sulfasalazine and its metabolites on the generation of reactive oxygen species (1987) Gut, 28, pp. 190-195; Pronai, L., Yukinobu, I., Lang, I., Feher, J., The oxygen centered radical scavenging activity of sulfasalazine and its metabolites. A direct protection of bowel (1992) Acta Physiol. Hung, 80, pp. 317-323; Rauch, K., Weilland, H., Behandlung der radiogenen kolitis mit salisilazosulfapyridin (azusulfidine) (1972) Strahlentherapie, 143, pp. 660-663; Kilic, D., Ozenirler, S., Egenhan, I., Dursun, A., Sulfasalazine decreases acute gastrointestinal complications due to pelvic radiotherapy (2001) Ann. Pharmacother, 35, pp. 806-810; Kilic, D., Ozenirler, S., Egenhan, I., Dursun, A., Double-blinded, randomized, placebo-controlled study to evaluate the effectiveness of sulphasalazine in preventing acute gastrointestinal complications due to radiotherapy (2000) Radiother. Oncol, 57, pp. 125-129; Lee, Y.S., Kang, S.K., Kim, T.H., Myong, N.H., Jang, J.J., Species, strain and sex differences in susceptibility to gamma radiation combined with diethylnitrosamine (1998) Anticancer Res, 18, pp. 1105-1109; Calabrese, E.J., Baldwin, L.A., The effects of gamma rays on longevity (2000) Biogerontology, 1, pp. 309-319; Ghosh, M.N., (1984) Fundamentals of Experimental Pharmacology, pp. 153-157. , 2nd edn. Scientific Book Agency, Calcutta, India; Geigy, J. R. (1956) Documents Geigy Scientific Tables. 5th edn. J. Board & Co. Ltd., Basle, UK, pp. 26-48; Uma Devi, P., Bisht, K.S., Vinitha, M., A comparative study of radioprotection by ocimum flavonoids and synthetic aminothiol protectors in the mouse (1998) Br. J. Radiol, 71, pp. 782-784; Savage, J.R.K., Classification and relationships of induced chromosomal structural changes (1976) J. Med. Genet, 12, pp. 103-122; Bender, M.A., Awa, A.A., Brooks, A.L., Evans, H.J., Groer, P.G., Littlefield, L.G., Pereira, C., Wachholz, B.W., Current status of cytogenetic procedures to detect and quantify previous exposures to radiation (1988) Mutat. Res, 196, pp. 103-159; Schmid, W., Chemical mutagen testing on in vivo somatic cells (1973) Agents Actions, 3, pp. 77-85; Schmid, W., The micronucleus test (1979) Mutat. Res, 31, pp. 9-15; Wijewickreme, A.N., Krejpcio, Z., Kitts, D.D., Hydroxyl scavenging activity of glucose, fructose and ribose-lysine model Maillard products (1999) J. Food Sci, 64, pp. 457-461; Cole, R.J., Tylor, N., Cole, J., Arlett, C.F., Short-term tests for transplacentally active carcinogens. I. Micronucleus formation in fetal and maternal mouse erythroblasts (1981) Mutat. Res, 80, pp. 141-157; Jagetia, G.C., Ganapathi, N.G., Treatment of mice with a herbal preparation (Liv. 52) reduces the frequency of radiation-induced chromosome damage in bone marrow (1991) Mutat. Res, 253, pp. 123-126; Jagetia, G.C., Venkatesha, V.A., Reddy, T.K., Naringin, a citrus flavonone, protects against radiation-induced chromosome damage in mouse bone marrow (2003) Mutagenesis, 18, pp. 337-343; Carrano, A.V., Heddle, J.A., The fate of chromosome aberrations (1973) J. Theor. Biol, 38, pp. 289-304; Sasaki, H., Lethal sectoring, genomic instability, and delayed division delay in HeLa S3 cells surviving alpha- or X-irradiation (2004) J. Radiat. Res, 45, pp. 497-508; Fenech, M., Cytokinesis-block micronucleus cytome assay (2007) Nat. Protoc, 2, pp. 1084-1104; Hofer, M., Mazur, L., Pospisil, M., Weiterova, L., Znojil, V., Radioprotective action of extracellular adenosine on bone marrow cells in mice exposed to gamma rays as assayed by the micronucleus test (2000) Radiat. Res, 154, pp. 217-221; Yuhas, J.M., Storer, J.B., Chemoprotection against three modes of radiation death (1969) Int. J. Radiat. Biol, 15, pp. 233-237; Uma Devi, P., Prasanna, P.G.S., Radioprotective effect of combinations of WR-2721 and mercaptopropionylglycine on mouse bone marrow chromosomes (1990) Radiat. Res, 124, pp. 165-170; Gupta, R., Uma Devi, P., Protection of mouse chromosomes against whole-body gamma irradiation by SH-compounds (1986) Br. J. Radiol, 59, pp. 625-627; Thomas, B., Uma Devi, P., Chromosome protection by WR-2721 and MPG-single and combination treatments (1987) Strahlenther Onkol, 163, pp. 807-810; Ganasoundari, A., Uma Devi, P., Rao, B.S.S., Enhancement of bone marrow radioprotection and reduction of WR-2721 toxicity by Ocimum sanctum (1998) Mutat. Res, 397, pp. 303-312; Jagetia, G.C., Aruna, R., The herbal preparation abana protects against radiation-induced micronuclei in mouse bone marrow (1997) Mutat. Res, 393, pp. 157-163; Chaubey, R.C., Bhilwade, H.N., Joshi, B.N., Chauhan, P.S., Studies on the migration of micronucleated erythrocytes from bone marrow to the peripheral blood in irradiated Swiss mice (1993) Int. J. Radiat. Biol, 63, pp. 239-245; Sudheer Kumar, M., Unnikrishnan, M.K., Uma Devi, P., Effect of 5-aminosalicylic acid on radiation-induced micronuclei in mouse bone marrow (2003) Mutat. Res, 527, pp. 7-14; Grzelinska, E., Bartkowiak, A., Bartosz, G., Leyko, W., Effect of •OH scavengers on radiation damage to the erythrocyte membrane (1982) Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med, 41, pp. 473-481; Joshi, R., Kumar, S., Unnikrishnan, M., Mukherjee, T., Free radical scavenging reactions of sulfasalazine, 5-aminosalicylic acid and sulfapyridine: Mechanistic aspects and antioxidant activity (2005) Free Radic. Res, 39, pp. 1163-1172; Bishop, J.B., Witt, K.L., Gulati, D.K., MacGregor, J.T., Evaluation of the mutagenicity of the anti-inflammatory drug salicylazosulfapyridine (SASP) (1990) Mutagenesis, 5, pp. 549-554; Iatropoulos, M.J., Williams, G.M., Abdo, K.M., Kari, F.W., Hart, R.W., Mechanistic studies on genotoxicity and carcinogenicity of salicylazosulfapyridine an anti-inflammatory medicine (1997) Exp. Toxicol. Pathol, 49, pp. 15-28; Uma Devi, P., Nagarathnam, A., Rao, B.S.S., DNA damage and repair (2000) Introduction to Radiation Biology, pp. 52-64. , Churchill Livingstone Pvt. Ltd, New Delhi, India, pp; Sasaki, M.S., Matsubara, S., Free radical scavenging in protection of human lymphocytes against chromosome aberration formation by gamma-ray irradiation (1977) Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med, 32, pp. 439-445; Roots, R., Okada, S., Protection of DNA molecules of cultured mammalian cells from radiation-induced single-strand scissions by various alcohols and SH compounds (1972) Int J. Radiat. Biol. Relat. Stud. Phys. Chem. Med, 21, pp. 329-342; Okada, S., Nakamura, N., Sasaki, K., Radioprotection of intracellular genetic material (1983) Radioprotection and Anticarcinogens, pp. 339-356. , Nygaard, O. F. and Simic, M. G, eds, Academic Press, New York, pp; Shimoi, K., Masuda, S., Shen, B., Furugori, M., Kinae, N., Radiation protection effect of antioxidative plant flavonoids in mice (1996) Mutat. Res, 350, pp. 153-161; Abraham, S.K., Sarma, L., Kesavan, P.C., Protective effects of chlorogenic acid, curcumin and β-carotene against c-radiation-induced in vivo chromosomal damage (1993) Mutat. Res, 303, pp. 109-112; Sarma, L., Kesavan, P.C., Protective effects of vitamin C and E against γ-ray-induced chromosomal damage in mouse (1993) Int. J. Radiat. Biol, 63, pp. 759-764; Umegaki, K., Ikegami, S., Inoue, K., Ichikawa, T., Kobayashi, S., Soeno, N., Tomebachi, K., Beta-carotene prevents X-ray induction of micronuclei in human lymphocytes (1994) Am. J. Clin. Nutr, 59, pp. 409-412; O'Neill, P., Fielden, E.M., Primary free radical processes in DNA (1993) Advances in Radiation Biology, pp. 53-120. , Lett, J. T. and Sinclair, W. K, eds, Academic Press, New York, pp; Uma Devi, P., Ganasoundari, A., Rao, B.S.S., Srinivasan, K.K., In vivo radioprotection by ocimum flavonoids: Survival of mice (1999) Radiat. Res, 151, pp. 74-78; Maisin, J.R., Albert, C., Henry, A., Reduction of short-term radiation lethality by biological response modifiers given alone or in association with other chemical protectors (1993) Radiat. Res, 135, pp. 332-337; Michalowski, A.D., On radiation damage to normal tissue and treatment (1994) Acta Oncol, 33, pp. 139-157; Satyamitra, M., Uma Devi, P., Murase, H., Kagiya, V.T., In vivo postirradiation protection by a vitamin E analog, alpha-TMG (2003) Radiat. Res, 160, pp. 655-661; Farooqi, Z., Kesavan, P.C., Radioprotection by caffeine pre- and post-treatment in the bone marrow chromosomes of mice given whole-body c-irradiation (1992) Mutat. Res, 269, pp. 225-230; Gout, P.W., Buckley, A.R., Simms, C.R., Bruchovsky, N., Sulfasalazine, a potent suppressor of lymphoma growth by inhibition of the x(c)-cystine transporter: A new action for an old drug (2001) Leukemia, 15, pp. 1633-1640; Chung, W.J., Lyons, S.A., Nelson, G.M., Hamza, H., Gladson, C.L., Gillespie, G.Y., Sontheimer, H., Inhibition of cystine uptake disrupts the growth of primary brain tumors (2005) J. Neurosci, 25, pp. 7101-7110; Doxsee, D.W., Gout, P.W., Kurita, T., Sulfasalazine-induced cystine starvation: Potential use for prostate cancer therapy (2007) Prostate, 67, pp. 162-171; Fischer-Nielsen, A., Poulsen, H.E., Loft, S., 8-Hydroxydeoxyguanosine in vitro: Effects of glutathione, ascorbate and 5-aminosalicylic acid (1992) Free Radic. Biol. Med, 13, pp. 121-126

PY - 2008

Y1 - 2008

N2 - 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. © The Author 2008. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved.

AB - 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. © The Author 2008. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved.

U2 - 10.1093/mutage/gen005

DO - 10.1093/mutage/gen005

M3 - Article

VL - 23

SP - 285

EP - 292

JO - Mutagenesis

JF - Mutagenesis

SN - 0267-8357

IS - 4

ER -