Honors College Thesis

 

Genotyping Cytochrome P450 1B1*3(Phase I) and Glutathione S-transferase Mu 1 null (Phase II), Metabolizing Enzymes in a [14C]Benzo[a]pyrene Human Micro Dosing Study Public Deposited

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https://ir.library.oregonstate.edu/concern/honors_college_theses/ng451q90d

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  • Polycyclic Aromatic Hydrocarbons (PAHs) have been studied for their carcinogenic toxicity. PAHs are formed by incomplete carbon combustion. Benzo[a]pyrene (BaP) is an IARC classified Class 1 Human carcinogenic PAH. New studies are conducted to gain a better understanding of PAHs and how to reduce exposure. Glutathione S-transferase M 1 (GSTM1 null) and Cytochrome P4501B1*1/*3 (CYP1B1*1/*3) polymorphisms have been implicated for their increased cancer risk through PAH oxidative metabolism. In this study, DNA was extracted from blood samples taken from study participants given one dose of 14C-BaP. DNA was genotyped for GSTM1 null and CYP1B1*1/*3 in order to compare to the same individual’s BaP metabolic profiles measured on accelerator mass spectrometry UPLC/AMS). Identifying major metabolites associated with specified SNPs can help in estimating carcinogenic risk. Of the ten participants, BaP021 and BaP023 are both positive for GSTM1. The rest of the eight participants are GSTM1 nulls. BaP21, 27, and 31 are wild type alleles while participants BaP23, 24, 25, 41 are heterozygotes, and BaP22 is homozygous. There were no significant trend indicating that participants with CYP1B1*1/*1 allele have increased CYP1B1 expression. The data did not demonstrate that participants with CYP1B1*1/*1 allele detoxified B[a]P more efficiently.
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