BETA-CAROTENE AS A MODULATOR OF CHROMOSOMAL-ABERRATIONS INDUCED IN MOUSE BONE-MARROW CELLS

The inhibitory effects of beta-carotene on cyclophosphamide (CPA)-induced chromosomal aberrations in mouse bone marrow cells were investigated. Male Balb C mice, 8-10 weeks old, were treated with beta-carotene (0.5, 1.0, 2.0, 5.0, 10, 25, 50, 100, and 200 mg/kg) or with corn oil (0.05 ml/10 g b.w.) by gavage for 5 consecutive days. Four hours after the last treatment with or without beta-carotene, the animals were intraperitoneally injected with CPA and killed 24 hr later for cytological preparations and analysis. The results obtained show that beta-carotene provides significant protection against the clastogenicity of CPA. The maximum reduction in the frequency of aberrant metaphases (26.9%) and in total number of chromosomal aberrations were observed when beta-carotene was used at 50 mg/kg. Nevertheless, no direct dose-response relationship was detected, suggesting that beta-carotene might act through different mechanisms at differents doses. The results obtained in animals studies have served as part of the basis for the human intervention studies now underway to determine if beta-carotene does indeed function as a chemopreventive agent in human nutrition.