Comparative studies on genotoxicity and antigenotoxicity of natural and synthetic beta-carotene stereoisomers.

To evaluate the practical value of natural beta-carotene (NbetaC) and to elucidate the apparent discrepancy between epidemiological observations and intervention trials on the role of beta-carotene (betaC) in tumor prevention, the genotoxicity and the antigenotoxicity of NbetaC and synthetic betaC crystal (SbetaCC) stereoisomers were studied comparatively using chromosome aberration analysis and the micronucleus test in human lymphocytes in vitro. NbetaC was extracted from the halotolerant algae Dunaliella salina. The NbetaC crystal (NbetaCC) preparation is about 70% all-trans (TbetaC) and 8% 9-cis (CbetaC). The NbetaC oil (NbetaCO) preparation is about 40% all-trans and 38% 9-cis. SbetaCC is more than 97% all-trans, and the 9-cis can not be detected. The mixture of betaC (betaCM) preparation is 74% SbetaCC and 26% NbetaC. Our results show no genotoxicity of 1-30 microg/ml NbetaCC, but this concentration of NbetaCC inhibited significantly gamma-ray-induced micronucleus formation in human lymphocytes in vitro. One to thirty microg/ml NbetaCO was most effective against both gamma-ray-induced and spontaneous micronucleus formation. However, no influence of NbetaCO on spontaneous chromosome aberrations in human lymphocytes in vitro was observed. NbetaCO suppressed significantly mitomycin C (MMC)-induced chromosome aberrations. One to thirty microg/ml SbetaCC induced a dose-dependent increase in micronucleus frequency, and also inhibited gamma-ray-induced micronucleus formation. No effect of betaCM on spontaneous chromosome aberrations was found. One to thirty microg/ml betaCM is more effective against MMC-induced chromosome aberrations than NbetaCO. These results suggest that CbetaC might play a critical role in the genotoxicity and antigenotoxicity of SbetaCC and NbetaC. The genotoxic activity of SbetaCC might be involved in carcinogenesis. NbetaC or betaCM could be of practical value in tumor prevention and supplementary treatment.