Mutat Res. 2008 Dec 8;657(2):98-104. Epub 2008 Aug 12.
Naturally occurring chlorophyll derivatives inhibit aflatoxin B1-DNA adduct formation in hepatoma cells.
College of Pharmacy, School of Nutrition and Health Science, Taipei Medical University, Taipei 110, Taiwan.
The inhibitory effects of four chlorophyll derivatives (chlorophyllide [Chlide] a and b and pheophorbide [Pho] a and b) on aflatoxin B1 (AFB1)-DNA adduct formation, and on the modulation of hepatic glutathione S-transferase (GST) were evaluated in murine hepatoma (Hepa-1) cells.
Enzyme-linked immunosorbent assay showed that pretreatment with Chlide or Pho significantly reduced the formation of AFB1-DNA adducts, and that Pho was the most potent inhibitor.
However, wash-out prior to adding AFB1 totally eliminated inhibition by Childe and partially eliminated inhibition by Pho, indicating that the inhibitory effect of Chlide, and to some extent Pho, was mediated through direct trapping of AFB1.
Furthermore, spectrophotometric analysis showed that Pho treatment could increase GST activity in Hepa-1 cells.
These observations indicate that the chlorophyll derivatives studied may attenuate AFB1-induced DNA damage in the Hepa-1 cell by direct trapping of AFB1.
Pho provided additional protection not only by direct trapping, but also by increasing GST activity against hepatic AFB1 metabolites.
PMID: 18775795 [PubMed - indexed for MEDLINE]
J Toxicol Clin Toxicol. 2003;41(2):195-204.
Dietary aflatoxin exposure and chemoprevention of cancer: a clinical review.
Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon 97331-6502, USA. firstname.lastname@example.org
Exposure to dietary aflatoxins is considered to be an important risk factor for the development of hepatocellular carcinoma in certain regions of the world. Significant advances have recently been made in understanding the clinical toxicology of aflatoxins.
These include the development and validation of biomarkers of exposure and genotoxic effect.
These biomarkers are currently being utilized to explore the potential that pharmaceutical interventions may have in modifying the toxicokinetics of dietary aflatoxin exposure.
Preliminary results of clinical trials with the drug oltipraz suggest that it may modify the genotoxic effects of aflatoxin B1 by inhibiting bioactivation pathways and stimulating detoxification pathways.
More recent results of a clinical trial with chlorophyllin suggest that this drug may have a role in preventing dietary exposure to aflatoxin B1 by reducing its oral bioavailability.
The preliminary results of these chemoprevention studies may ultimately have implications for cancer prevention in high-risk populations in the future.
PMID: 12733859 [PubMed - indexed for MEDLINE]