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Chlorophyllin chemoprevention against Dibenzo[a,l]pyrene-initiated multi-organ carcinogenesis in the rainbow trout model

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dc.contributor.advisor Bailey, George S.
dc.creator Pratt, Mary Margaret
dc.date.accessioned 2012-07-17T19:58:29Z
dc.date.available 2012-07-17T19:58:29Z
dc.date.copyright 2003-01-22
dc.date.issued 2003-01-22
dc.identifier.uri http://hdl.handle.net/1957/31143
dc.description Graduation date: 2003 en_US
dc.description.abstract Chlorophyllin (CHL), a water-soluble derivative of the green plant pigment, chlorophyll, is an effective antimutagen and anticarcinogen in various model systems when used as a modulator against a class of carcinogens that, in general, have a structure consisting of at least three fused rings. Dibenzo[a,l]pyrene (DBP), an extremely potent environmental carcinogen, has been isolated from urban air samples, tobacco smoke, and coal smoke condensate. A study was conducted to evaluate the complex interrelationships among dietary DBP doses with co-exposure to a range of CHL doses. In order to achieve adequate statistical power in the generation of multiple dose-response curves, this dose-dose matrix experiment utilized over 12,000 rainbow trout. The resulting DNA adducts were assessed and evaluated as biomarkers of exposure to discern their relationship with the final tumor outcome. CHL was highly effective in reducing DBP-initiated DNA adduct formation in the liver and stomach and strongly inhibited tumor formation in the liver (56-79% inhibition), stomach (30-68%), and swim bladder (over 80% at the highest DBP dose). Molecular dosimetry revealed adduct formation to be predictive of final tumor response in both organs regardless of CHL dose. Other parameters evaluated were consistent with CHL-mediated protection. A clinical CHL preparation, evaluated in a human population subsequent to the seminal demonstration of CHL chemopreventive properties against AFB₁ in trout (1), revealed CHL to be just as effective in reducing biomarkers of alfatoxin exposure to humans (2). Dietary administration of this clinical preparation along with DBP in the rainbow trout demonstrated CHL protective capacity against DBP-initiated multi-organ DNA adduct formation and final tumor incidence. Sucrose was evaluated, deemed unlikely to be sequestered in a complex with CHL, and was used as a control in a pharmacokinetic study evaluating the biodistribution of DBP with and without CHL. The results provide evidence against a non-specific masking mechanism for CHL-mediated blocking of DBP (or aflatoxin)-initiated tumorigenesis. CHL at multiple doses provided significant protection against multi-dose DBP-initiated DNA adduction and tumor formation in multiple organs. CHL-mediated protection, primarily by reduced carcinogen biouptake and consistent with a complexation mechanism, is supported by these results. en_US
dc.language.iso en_US en_US
dc.subject.lcsh Chlorophyllin -- Therapeutic use -- Effectiveness en_US
dc.subject.lcsh Antimutagens en_US
dc.subject.lcsh Benzopyrene -- Carcinogenicity en_US
dc.subject.lcsh Cancer -- Chemoprevention en_US
dc.subject.lcsh Rainbow trout -- Diseases -- Prevention en_US
dc.title Chlorophyllin chemoprevention against Dibenzo[a,l]pyrene-initiated multi-organ carcinogenesis in the rainbow trout model en_US
dc.type Thesis/Dissertation en_US
dc.degree.name Doctor of Philosophy (Ph. D.) in Toxicology en_US
dc.degree.level Doctoral en_US
dc.degree.discipline Agricultural Sciences en_US
dc.degree.grantor Oregon State University en_US
dc.description.digitization File scanned at 300 ppi (Monochrome, 8-bit Grayscale) using ScandAll PRO 1.8.1 on a Fi-6670 in PDF format. CVista PdfCompressor 4.0 was used for pdf compression and textual OCR. en_US
dc.description.peerreview no en_us

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