Effect of 5-aminosalicylic acid on radiation-induced micronuclei in mouse bone marrow.
5-Aminosalicylic acid (5ASA), a prescribed drug for ulcerative colitis, is a potent scavenger of oxygen-derived free radicals. The present study was undertaken to ascertain its ability to protect against radiation-induced damage. The drug dose-dependent effect, optimum time of drug administration and radiation dose-dependent effect (0-4 Gy) on in vivo radiation protection against micronuclei induction in polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) were studied in the bone marrow of mice. Intraperitoneal injection of 10-125 mg/kg of the drug 30 min before whole body irradiation with 3 Gy produced a significant reduction in the frequency of micronucleated erythrocytes at 24 h after exposure. The optimum dose for protection without drug toxicity was 25 mg/kg body weight. Injection of 25 mg/kg of the drug 60 or 30 min before or within 15 min after 3 Gy whole body gamma-irradiation resulted in a significant decrease in the radiation-induced PCE and NCE with micronuclei (MPCE and MNCE) and an increase in the ratio of PCE to NCE (P/N), at 24 h post-irradiation. Maximum effect was seen when the drug was administered 30 min before irradiation. Therefore, to study the radiation dose-response, mice were pre-treated with 25 mg/kg of 5ASA 30 min before 1-4 Gy of gamma-irradiation. Radiation increased the MN frequency linearly (r(2)=0.99) with dose. Pre-treatment with 5ASA significantly reduced the MN counts to 40-50% of the radiation (RT) alone values, giving a dose modification factor (DMF) of 2.02 (MPCE) and 2.53 (MNCE). Irradiation resulted in a dose-dependent decline in the P/N ratio at all the doses of radiation studied. 5ASA produced a significant increase in the P/N ratio from that of irradiated controls, at all doses of radiations tested. These results show that 5ASA protect mice against radiation-induced MN formation and mitotic arrest.
Sudheer Kumar
M
M
Department of Pharmacology, College of Pharmaceutical Sciences, Manipal 576119, India.
Unnikrishnan
M K
MK
Uma Devi
P
P
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000528:radiation effects*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D005720:Gamma Rays; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects* / Q000528:radiation effects*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013997:Time Factors; D014916:Whole-Body Irradiation
D011837:Radiation-Protective Agents; D019804:Mesalamine