Protective Effect Of β-Carotene On Genetic Damage In Bone Marrow Cells Of Mice By Mitomycin-C

OBJECTIVE: -carotene( C) is one kind of carotenoids and widely present in food supply such as fruit and vegetable. As an antioxidant, the effect of P C in tumor prevention and inhibition is widely concerned. However, there are few reports about its modulating effect in reducing toxicity of chemotherapeutic drug. The objective of this study is to test whether P C can reduce the genetic damage induced by mitomycin-C(MMC) in bone marrow cells of mice and pursue its possible mechanism. It is very significant for understanding the mechanism of C in reducing toxicity of alkylating chemotherapeutic drug and directing drug-using in tumor therapy.METHODS AND RESULTS: In the present work, the single cell gel electrophoresis (SCGE) assay and chromosomal aberrations (CA) test were used. Two batches of mice were primed orally with P C in concentrations of 3 and 30mg/kg b.w. for 8 days and then followed by an acute treatment with MMC(2 mg/kg b.w.; i.p.) on day 9. A part of mice from each batch were killed 12h later after administration and others were done 24h later. The bone marrow cells were isolated to be tested by SCGE and CA respectively. In addition, to study the repairing effect of damaged DNA, the bone marrow cells of two batches mice were isolated at 3h, 6h, 12h, 24h respectively after MMC injection and be tested by SCGE. The result showed: The DNA damage level and the chromosomal aberration rate of two dosages of P C group are lower significantly than that of the positive control group and showed adose-dependent decrease. Both of two dosages of β C groups showed faster than the positive group in DNA damage-repairing. The protective effect of low-dosage β C group began at 6h later after administration and the high-dosage P C show protective effect at all sampling time.CONCLUSION: 1. P C can modulate significantly the genetic damage induced by MMC in bone marrow cells of mice; 2. β C can accelerate the repairing process of damaged DNA in vivo ; 3.The action of two dosages of P C in modulating MMC-induced DNA damage may not be same completely: low-dosage P C act protective function only by accelerating the repairing process of damaged DNA, but high-dosage P C done it by accelerating the DNA-repairing process and inhibiting directly the DNA damage induced by MMC; 4.SCGE and CA has different superiority in test of genetic damage respectively. The combination of two methods would improve the accuracy in checking of mutagen and testing of the genotoxicity of agent.