Influence of chlorpromazine, bleomycin and WR-2721 singly or in combination on the formation of radiation-induced micronuclei in mice bone marrow.
OBJECTIVE
Radiotherapy of tumors is often accompanied by inadvertant side effects on the normal tissues after completion of the treatment, which may later on result in the development of secondary neoplasia. Aim was to investigate the effect of combination of radiosensitizing agents in combination with a radioprotector on the frequency of micronuclei in mouse bone marrow and to find out whether the administration of combination of radiosensitizing agents in combination with a radioprotective drug before irradiation will offer any significant advantage over the drugs used singly.


METHODS
Female BALB/c mice were divided into 8 groups according to the treatment they received viz. 1. DDW (double distilled water), 2. chlorpromazine (CPZ) 10 mg/kg body-weight, 3. CPZ 15 mg/kg body-weight 4. bleomycin (BLM), 5. WR-2721, 6. CPZ (10 mg) + WR-2721, 7. CPZ (15 mg) + WR-2721, 8. BLM + WR-2721. After 30 min of drug/s administration the animals were exposed to either 0 or 4 Gy of 60Co g-radiation. The animals were killed at 24 h post-irradiation by cervical dislocation and the micronuclei were prepared according to the method described by Jagetia [17].


RESULTS
The administration of CPZ (10 or 15 mg) alone increased the frequency of micronuclei significantly when compared to the DDW treatment. The exposure of mice with 4 Gy resulted in a significant increase in the frequency of micronuclei compared to the concurrent control groups. The frequency of micronuclei increased significantly in CPZ (15 mg) and BLM + irradiated groups. However, treatment with WR-2721 before irradiation reduced the frequency of micronuclei by approximately 50% of the DDW + irradiated group. A further reduction in the frequency of micronuclei was observed when WR-2721 was combined with CPZ (10 and 15 mg) before irradiation. A combination of BLM with WR-2721 also resulted in a nonsignificant reduction in the frequency of micronuclei.
Jagetia
G C
GC
Department of Radiobiology, Kasturba Medical College, Manipal, India.
D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D001761:Bleomycin / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects* / Q000528:radiation effects* / Q000648:ultrastructure; D002746:Chlorpromazine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005720:Gamma Rays; D051379:Mice; D008807:Mice, Inbred BALB C; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects* / Q000528:radiation effects* / Q000648:ultrastructure; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D011838:Radiation-Sensitizing Agents; D001761:Bleomycin; D004999:Amifostine; D002746:Chlorpromazine