This core is to establish a facility to carry out laboratory investigations on oxygen free radical damage for the Seattle Gastrointestinal Program Project. Our goal is to ascertain whether damage or mutations resulting from oxygen free radicals accumulate in pre- cancerous tissues or in tumors. The quantitation of oxygen free radial damage to DNA will be carried out by measuring the content of 8-oxo- deoxyguanosine and 5-hydroxycytidine in DNA from cells obtained from pancreatic cancer, ulcerative colitis, and colon cancer. 8-oxo- deoxyguanosine is a well documented marker of oxygen free radical damage to DNA. We have presented evidence that 5-OH-deoxycytidine is produced by oxygen free radicals and is highly mutagenic. Both of these adducts will be quantitated by high pressure liquid chromatography coupled with electrochemical detection. The quantitation of mutations due to oxygen free radical damage to DNA will be established by measuring the frequency of CC>TT mutations in a target gene, DNA polymerase-beta in cells obtained in each of the projects in this Program; the CC>TT mutations can be diagnostic of oxygen free radical damage to DNA and can be quantitated at a frequency of 10/-6 by a new PCR based mismatched assay. Together these studies on oxygen free radical damage and mutations provide a spectrum of probes to analyze the contribution of oxygen free radical damage to these important cancers.
| Passarelli, Michael N; Newcomb, Polly A; Makar, Karen W et al. (2015) Blood lipids and colorectal polyps: testing an etiologic hypothesis using phenotypic measurements and Mendelian randomization. Cancer Causes Control 26:467-73 |
| Adams, Scott V; Newcomb, Polly A; Burnett-Hartman, Andrea N et al. (2014) Rare circulating microRNAs as biomarkers of colorectal neoplasia. PLoS One 9:e108668 |
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| Burnett-Hartman, Andrea N; Newcomb, Polly A; Potter, John D et al. (2013) Genomic aberrations occurring in subsets of serrated colorectal lesions but not conventional adenomas. Cancer Res 73:2863-72 |
| Burnett-Hartman, Andrea N; Passarelli, Michael N; Adams, Scott V et al. (2013) Differences in epidemiologic risk factors for colorectal adenomas and serrated polyps by lesion severity and anatomical site. Am J Epidemiol 177:625-37 |
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| Adams, Scott V; Newcomb, Polly A; Burnett-Hartman, Andrea N et al. (2011) Circulating 25-hydroxyvitamin-D and risk of colorectal adenomas and hyperplastic polyps. Nutr Cancer 63:319-26 |
| Chia, Victoria M; Newcomb, Polly A; Lampe, Johanna W et al. (2007) Leptin concentrations, leptin receptor polymorphisms, and colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev 16:2697-703 |
| O'Sullivan, Jacintha; Risques, Rosa Ana; Mandelson, Margaret T et al. (2006) Telomere length in the colon declines with age: a relation to colorectal cancer? Cancer Epidemiol Biomarkers Prev 15:573-7 |
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