Sahu K, Das R K
Environmental Mutagenesis Unit, School of Life Sciences, Sambalpur University, Jyotivihar, Orissa, India.
Food Chem Toxicol. 1994 Oct;32(10):911-5. doi: 10.1016/0278-6915(94)90089-2.
Clofazimine (CLF), an antileprosy drug, has earlier been proved to be clastogenic in mice in vivo. It is an important constituent of the triple-drug regimen recommended by WHO for the treatment of leprosy. In this study the protective role of vitamins A and C (vit A and vit C) against the clastogenic effect of CLF in mouse bone marrow cells has been evaluated. Two doses (20 and 40 mg/kg) of vit C and two doses (2500 and 5000 IU/kg) of vit A were tested against a dose of 40 mg CLF/kg. The drug alone induced chromosomal aberrations of about 8 times the control value. Neither of the doses of vit C exhibited any clastogenic effect and, when administered simultaneously with CLF, both reduced the effect of CLF very significantly, the higher dose reducing chromosomal aberrations almost to the control value. Conversely, both doses of vit A, when administered alone, brought about significant increases in chromosome aberrations over the control value; the higher, but not the lower dose, given simultaneously with CLF, minimized the effect of CLF significantly but not as greatly as vit C. A scavenging effect of the vitamins, removing free radicals produced by CLF, is assumed to be responsible for modulation of the clastogenic effect of CLF.
氯法齐明（CLF）是一种抗麻风病药物，此前已被证明在小鼠体内具有致断裂作用。它是世界卫生组织推荐的治疗麻风病的三联药物疗法的重要组成部分。在本研究中，评估了维生素A和维生素C（维生素A和维生素C）对CLF在小鼠骨髓细胞中致断裂作用的保护作用。针对40 mg/kg的CLF剂量，测试了两种剂量（20和40 mg/kg）的维生素C和两种剂量（2500和5000 IU/kg）的维生素A。单独使用该药物诱导的染色体畸变约为对照值的8倍。两种剂量的维生素C均未表现出任何致断裂作用，并且在与CLF同时给药时，两者均非常显著地降低了CLF的作用，较高剂量几乎将染色体畸变降低至对照值。相反，两种剂量的维生素A单独给药时，导致染色体畸变比对照值显著增加；较高剂量（而非较低剂量）与CLF同时给药时，显著降低了CLF的作用，但不如维生素C降低得明显。假定维生素的清除作用可清除CLF产生的自由基，这是调节CLF致断裂作用的原因。
