Aflatoxin B1-induced toxicity in HepG2 cells inhibited by carotenoids: morphology, apoptosis and DNA damage.
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 beta-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 beta-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 beta-carotene are protected from the toxic effects of AFB1 at both the cellular and molecular levels.
Department of Biotechnology, Durban Institute of Technology, Durban 4000, South Africa.
Lalini
L
Reddy
Bharti
B
Odhav
Kanti
K
Bhoola
D016604:Aflatoxin B1 / Q000633:toxicity*; D017209:Apoptosis; D002338:Carotenoids / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects; D018736:DNA Adducts / Q000187:drug effects; D004249:DNA Damage; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D000077276:Lycopene; D009152:Mutagenicity Tests; D019207:beta Carotene / Q000494:pharmacology
D018736:DNA Adducts; D019207:beta Carotene; D002338:Carotenoids; D016604:Aflatoxin B1; D000077276:Lycopene