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Lalini Reddy, Bharti Odhav, Kanti Bhoola

Aflatoxin B₁-induced toxicity in HepG2 cells inhibited by carotenoids: morphology, apoptosis and DNA damage

Keywords: aflatoxin B1, aflatoxin B1-N7-guanine adduct, ?-carotene, DNA fragment-end labeling, HepG2, lycopene, p53 tumor suppressor gene

Aflatoxin B₁ (AFB₁) is a fungal toxin that has been associated with primary hepatocellular carcinoma (HCC) in humans. This study was undertaken to determine the cellular and molecular mechanisms by which the antioxidants ?-carotene and lycopene inhibit AFB₁-induced toxic changes in human hepatocytes (HepG2 cells). An in vitro system was optimized to test the chemoprotective effects of lycopene and ?-carotene on HepG2 cells exposed to different concentrations of AFB₁. Ultrastructurally, HepG2 cells cultured in the presence of AFB₁ showed mitochondrial damage, nuclear condensation and a loss of cell-to-cell contact; the latter was reflected in the observation of dysfunctional gap junctions, resulting in a loss of cell-to-cell communication. At the genomic level, AFB₁ formed AFB₁-N7-guanine adducts, caused apoptotic cell death and suppressed p53 protein expression. In the presence of the carotenoids, survival of cells exposed to AFB₁ was increased, and there was also a significant increase in cellular mitochondrial activity. Our results demonstrate that HepG2 cells pretreated with lycopene and ?-carotene are protected from the toxic effects of AFB₁ at both the cellular and molecular levels.

Biological Chemistry, Walter de Gruyter

Print ISSN: 1431-6730
Volume: 387, 01/2006
Pages: 87 - 93

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