Aflatoxin: Causes Mutations in the p53 tumor suppressor gene (Chlorophyllin inhibits the mutagenicity of Aflatoxin)

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Aflatoxins are naturally occurring mycotoxins (mycotoxin is a toxic secondary metabolite produced by organisms of the fungi kingdom, commonly known as molds), that are produced by Aspergillus flavus and Aspergillus parasiticus.

Aflatoxin, the fungal carcinogen first identified in 1960, is now recognized as the prototypical laboratory carcinogen. It causes mutations in the p53 tumor-suppressor gene as well as ras mutations, which are involved in the majority of human cancers.   1

Aflatoxin is known to cause:

  • Liver cancer.  2  
  • Gallbladder cancer  3
  • Lung cancer  4  5
  • Osteogenic Sarcoma (bone tumor)  6

Liver cancer appears to be the cancer that is most susceptible to aflatoxin exposure.  A report entitled Global Burden of Aflatoxin-Induced Hepatocellular Carcinoma: A Risk Assessment published in 2010 found:  “Of the 550,000–600,000 new HCC cases worldwide each year, about 25,200–155,000 may be attributable to aflatoxin exposure. Most cases occur in sub-Saharan Africa, Southeast Asia, and China where populations suffer from both high HBV prevalence and largely uncontrolled aflatoxin exposure in food.”  7

Five research studies have been published showing that chlorophyllin has the potential to significantly reduce the risk of cancer induced by aflatoxin by binding to carcinogenic byproducts of aflatoxin metabolism and therefore, decreasing bioavailability of these cancer-causing chemicals.

Study 1 Abstract (1991)

Studies with the arabinose-resistant Salmonella forward mutation assay system were performed to determine the antimutagenic activity of chlorophyllin against the mutagenic activity of aflatoxin B1 (AFB1), 2-aminoanthracene (2AA), benzo[a]pyrene (BaP), N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) and solvent extracts of coal dust (CD), diesel emission particles (DE), airborne particles (AP), tobacco snuff (TS), black pepper (BP) and red wine (RW).  

Results showed that chlorophyllin, at concentrations of 2.5 mg/plate or less, completely or almost completely inhibited the mutagenicity of 2AA, AFB1, BaP, MNNG and solvent extracts of CD, DE and RW. With concentrations from 1.25 to 5 mg/plate, chlorophyllin inhibited over 50% of the mutagenicity of AP, TS and BP extracts.

Study 2 Abstract  (2001)

Chlorophyllin consumption at each meal led to an overall 55% reduction (P = 0.036) in median urinary levels of this aflatoxin biomarker compared with those taking placebo.

Thus, prophylactic interventions with chlorophyllin or supplementation of diets with foods rich in chlorophylls may represent practical means to prevent the development of hepatocellular carcinoma or other environmentally induced cancers.

Study 3 Abstract  (2003)

In the clinical trial, administration of CHL three times a day led to a 50% reduction in the median level of urinary excretion of aflatoxin-N(7)-guanine compared to placebo. This excreted DNA adduct biomarker is derived from the ultimate carcinogenic metabolite of aflatoxin B(1), aflatoxin-8,9-epoxide, and is associated with increased risk of developing liver cancer in prospective epidemiologic studies.

Compliance in the intervention was outstanding and no toxicities were observed. Thus, CHL has been found to be a safe and effective agent suitable for use in individuals unavoidably exposed to aflatoxins.

Study 4 Abstract  (2007)

Chemoprevention by chlorophyll (Chl) was investigated in a rat multi-organ carcinogenesis model. Twenty-one male F344 rats in three gavage groups (N = 7 rats each) received five daily doses of 250 microg/kg [(3)H]-aflatoxin B(1) ([(3)H]-AFB(1)) alone, or with 250 mg/kg chlorophyllin (CHL), or an equimolar amount (300 mg/kg) of Chl. 

CHL and Chl reduced the mean number of aberrant crypt foci per colon by 63% (P = 0.0026) and 75% (P = 0.0004), respectively.

These results show Chl and CHL provide potent chemoprotection against early biochemical and late pathophysiological biomarkers of AFB(1) carcinogenesis in the rat liver and colon.

Study 5 Abstract  (2009)

Chlorophyll (Chla) and chlorophyllin (CHL) were shown previously to reduce carcinogen bioavailability, biomarker damage, and tumorigenicity in trout and rats.

These findings were partially extended to humans, where CHL reduced excretion of aflatoxin B(1) (AFB(1))-DNA repair products in Chinese unavoidably exposed to dietary AFB(1).  Chla and CHL treatment each significantly impeded AFB(1) absorption and reduced Cmax and AUCs (plasma and urine) in one or more subjects.

These initial results provide AFB(1) pharmacokinetic parameters previously unavailable for humans, and suggest that Chla or CHL co-consumption may limit the bioavailability of ingested aflatoxin in humans, as they do in animal models.


Resources:

Life Extension – Chlorophyllin


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