Carcinogenesis Advance Access originally published online on January 16, 2006
Carcinogenesis 2006 27(6):1128-1133; doi:10.1093/carcin/bgi342
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ß-Carotene breakdown products enhance genotoxic effects of oxidative stress in primary rat hepatocytes
Department of Cell Biology, University of Salzburg, Hellbrunnerstrasse 34, A-5020 Salzburg, Austria 1 Children's Hospital, University of Ulm, Germany 2 Children's Hospital, University of Heidelberg, Germany and 3 Herzog-Julius Hospital for Rheumatology and Orthopedics, Kurhausstrasse 13-17, D-38667 Bad Harzburg, Germany
* To whom correspondence should be addressed. Tel: +43 662 8044 5782; Fax: +43 662 8044 144; Email: peter.eckl{at}sbg.ac.at
Since it has to be expected that individuals exposed to oxidative stress who take supplements of ß-carotene are simultaneously exposed to both ß-carotene cleavage products (CPs) and oxidative stress, and both exposures have been demonstrated to cause genotoxic effects in primary rat hepatocytes, cyto- and genotoxic effects on primary rat hepatocytes after supplementation of the medium with increasing concentrations of a CP mixture during exposure to oxidative stress by treatment with either DMNQ (2,3-dimethoxy-1,4-naphthoquinone) or hypoxia/reoxygenation (Hy/Reox) was investigated. The cytological endpoints analysed were the mitotic indices, the percentages of apoptotic and necrotic cells, the percentages of micronucleated (MN) cells and the number of chromosomal aberrations (CAs) and sister chromatid exchanges (SCE). The results obtained clearly demonstrate that the CP mixture enhances the genotoxic effects of oxidative stress exposure, whereas it had no effect at all on the endpoints of cytotoxicity studied. These results further support the hypothesis that CP might be responsible for the reported carcinogenic response in the beta-CArotene and Retinol Efficacy Trial (CARET) and Alpha-Tocopherol Beta-carotene Cancer prevention (ATBC) chemoprevention trials.
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