Chlorophyllin Chemoprevention in Trout Initiated by Aflatoxin B1 Bath Treatment: An Evaluation of Reduced Bioavailability vs. Target Organ Protective Mechanisms

doi:10.1006/taap.1999.8696

Toxicology and Applied Pharmacology

Volume 158, Issue 2, 15 July 1999, Pages 141-151

https://doi.org/10.1006/taap.1999.8696 Get rights and content

Abstract

Chlorophyllin (CHL) is known to inhibit DNA adduction and hepatocarcinogenesis in trout when administered at doses up to 4000 ppm in the diet with aflatoxin B₁ (AFB₁). The principal protective mechanism is believed to involve CHL:AFB₁ complex formation, which may reduce systemic carcinogen absorption. However, mechanisms operative within the target organ in situ have not been ruled out. The present study used alternative CHL and AFB₁ exposures as well as hepatic metabolism studies to distinguish these mechanisms. Duplicate lots of 150 rainbow trout each were initiated by brief water bath exposure to 0.1 ppm AFB₁, with or without 500 ppm CHL in the water. The addition of 500 ppm CHL to the water bath, under conditions where AFB₁ is calculated to be >99% sequestered as the CHL:AFB₁ complex, reduced hepatic AFB₁-DNA adduction by 95% and reduced hepatocarcinogenesis from 20.5% to 2%, compared with exposure to AFB₁ alone. Inclusion of 500 ppm CHL in the water bath also significantly reduced total body burden and hepatic levels of AFB₁ as well as AFB₂, a structural analogue of AFB₁ unable to directly form the 8,9-epoxide proximate electrophile but equally capable of complexing with CHL. By contrast, internal target organ CHL loading by pretreatment of trout with 4000 ppm dietary CHL for 7 days prior to (and 2 days following) AFB₁ waterbath exposure had no effect on AFB₁-DNA adduction or tumorigenicity. Dietary CHL up to 8000 ppm had no effect on hepatic CYP2K1, CYP1A, glutathione transferase, UDP-glucuronosyl transferase, or, with one exception, the relative ratios among hepatic AFB₁ metabolites in vivo. These results support the hypothesis that CHL:AFB₁ complex formation and reduced systemic AFB₁ bioavailability is a principal mechanism for CHL chemoprevention in this model and that in situ target organ inhibitory mechanisms are relatively insignificant.

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¹: Present address: Institute of Food Safety and Toxicology, Division of Biochemical and Molecular Toxicology, the Danish Veterinary and Food Administration, Copenhagen, Denmark.

²: To whom inquiries should be addressed at Marine/Freshwater Biomedical Science Center, Oregon State University, Corvallis OR 97331. Fax: (541) 737-7966; E-mail: [email protected].

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Regular ArticleChlorophyllin Chemoprevention in Trout Initiated by Aflatoxin B1 Bath Treatment: An Evaluation of Reduced Bioavailability vs. Target Organ Protective Mechanisms

Abstract

Anal. Biochem.

Mutat. Res.

Toxicol. Lett.

Cancer Lett.

J. Biol. Chem.

Toxicol. Appl. Pharmacol.

Mutat. Res.

Comp. Biochem. Physiol.

J. Biol. Chem.

Toxicol. Appl. Pharmacol.

Mutat. Res.

Cancer Lett.

Cancer Lett.

Gastroenterology

Mutat. Res.

Food Chem. Toxicol.

Mutat. Res.

UDP-glucuronyltransferase in perfused rat liver and in microsomes: Influence of phenobarbital and 3-methylcholanthrene

Eur. J. Biochem.

Current strategies of cancer prevention: 13th Sapporo Cancer Symposium

Cancer Res.

Dietary chlorophyllin is a potent inhibitor of aflatoxin B1 hepatocarcinogenesis in rainbow trout

Cancer Res.

Mechanisms of chlorophyllin anticarcinogenesis against aflatoxin B1: Complex formation with the carcinogen

Chem. Res. Toxicol.

Protection by chlorophyllin against the covalent binding of 2-amino-3-methylimidazo-(4,5-f)quinoline (IQ) to rat liver DNA

Carcinogenesis

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Int. J. Oncol.

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Carcinogenesis

Chemoprotective properties of chlorophyllin: Inhibition of aflatoxin B1 (AFB1)-DNA binding in vivo and antimutagenic activity against AFB1 and two heterocyclic amines in the salmonella mutagenicity assay

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Regular Article
Chlorophyllin Chemoprevention in Trout Initiated by Aflatoxin B₁ Bath Treatment: An Evaluation of Reduced Bioavailability vs. Target Organ Protective Mechanisms

Dietary chlorophyllin is a potent inhibitor of aflatoxin B₁ hepatocarcinogenesis in rainbow trout

Mechanisms of chlorophyllin anticarcinogenesis against aflatoxin B₁: Complex formation with the carcinogen

Chemoprotective properties of chlorophyllin: Inhibition of aflatoxin B1 (AFB₁)-DNA binding in vivo and antimutagenic activity against AFB₁ and two heterocyclic amines in the salmonella mutagenicity assay