β-carotene breakdown products enhance genotoxic effects of oxidative stress in primary rat hepatocytes

被引:26
作者
Alija, A. J.
Bresgen, N.
Sommerburg, O.
Langhans, C. D.
Siems, W.
Eckl, P. M.
机构
[1] Salzburg Univ, Dept Cell Biol, A-5020 Salzburg, Austria
[2] Univ Ulm, Childrens Hosp, Ulm, Germany
[3] Heidelberg Univ, Childrens Hosp, D-6900 Heidelberg, Germany
[4] Herzog Julius Hosp Rheumatol & Orthoped, D-38667 Bad Harzburg, Germany
关键词
D O I
10.1093/carcin/bgi342
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Since it has to be expected that individuals exposed to oxidative stress who take supplements of beta-carotene are simultaneously exposed to both beta-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.
引用
收藏
页码:1128 / 1133
页数:6
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