The role of polycyclic aromatic hydrocarbons in coal tar-induced genotoxicity and carcinogenicity /
Manufactured Gas Plant Residue (MGPR) is a byproduct of the
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
1996.
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| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=739793821&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | Manufactured Gas Plant Residue (MGPR) is a byproduct of the coal gasification process, and MGPRs are complex mixtures containing hundreds of organic and inorganic compounds. Because of a 100 year unrestricted release of MGPR into open sites, the risks associated with these coal tars are currently being evaluated by the Environmental Protection Agency and the electric power industry. Although MGPR is a known carcinogen, the questions concerning the relative toxicities of different coal tars have not been delineated. Among the hundreds of compounds within MGPR, polycyclic aromatic hydrocarbons (PAHs) constitute the most carcinogenic chemical class. PAHs both induce and are metabolized by the cytochrome p450 mixed-function monooxygenase system to reactive forms that are capable of covalently binding DNA. The weight of evidence from extensive experimentation in animal models suggests that DNA adduct formation is necessary but not sufficient for tumorigenesis. Additionally, DNA adducts provide an indication of biologically effective doses of chemical carcinogens. Administration of carcinogenic PAHs result in formation of various types of DNA adducts that differ between species, strain and tissues due to difference in metabolic activation and DNA repair processes. The three fundamental approaches to a toxicological study of mixtures are used in this study. The first approach involves exposure of a test system to the complete MGPR. Dose- response studies indicate that the carcinogenicity of MGPR at a dose of 1071 mg/kg was similar to that observed for lower doses of the carcinogen, benzo(a)pyrene (35.8 to 53.6 mg/kg). The second method investigates the toxicities of constituent chemical classes within complex mixtures thereby identifying which group of compounds elicit genotoxic responses. MGPR fractionation studies indicated that genotoxicity was primarily due to the PAH fractions and initial chemical analysis showed that benzo(a)pyrene was the most potent carcinogenic PAH in the MGPR. The comparative carcinogenic potency of the MGPR and a reconstituted mixture of PAHs which resemble the MGPR mixture was determined and the results showed that the reconstituted mixture was 11.3 times less active than the crude mixture. These results indicated that the unsubstituted PAHs were not responsible for MGPR-induced carcinogenicity. A third method for understanding the toxicity of complex mixtures involves comparing the toxicities of the mixtures with the effects of individual constituents or fractions. |
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| Item Description: | Vita. "Major Subject: Toxicology". |
| Physical Description: | xii, 154 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilms Inc. |
| Bibliography: | Includes bibliographical references: pages 119-153. |