title: Pyrimidine base damage is increased in women with BRCA mutations.
abstract: Oxidatively-induced DNA damage was measured in the DNA of WBC from two groups of women: carriers of a BRCA mutation, but asymptomatic for disease, and healthy controls. Two oxidatively induced lesions were measured: a formamide remnant of pyrimidine base and the glycol modification of thymine. These lesions, employed previously in studies of the effects of smoking, antioxidant usage and ovarian cancer, are proving valuable indicators of oxidative stress. The BRCA carriers of mutations, with no overt sign of cancer, nevertheless had significantly higher levels of DNA damage than the controls. The level measured for the formamide lesion was 5.9 ± 1.0 (femtomoles/μg of DNA ± SEM) compared with 2.4 ± 0.3 in controls. The level of the glycol lesion was 2.9 ± 0.4 compared with 1.8 ± 0.2 in controls. The experimental design utilized DNA from WBC and employed LC-MS/MS to detect the lesions.
authors.affiliation: Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Edwin E
authors.initials: EE
authors.lastname: Budzinski
authors.forename: Helen B
authors.initials: HB
authors.lastname: Patrzyc
authors.forename: Jean B
authors.initials: JB
authors.lastname: Dawidzik
authors.forename: Harold G
authors.initials: HG
authors.lastname: Freund
authors.forename: Peter
authors.initials: P
authors.lastname: Frederick
authors.forename: Heidi E
authors.initials: HE
authors.lastname: Godoy
authors.forename: Nicoleta C
authors.initials: NC
authors.lastname: Voian
authors.forename: Kunle
authors.initials: K
authors.lastname: Odunsi
authors.forename: Harold C
authors.initials: HC
authors.lastname: Box
mesh_terms: D016022:Case-Control Studies; D004247:DNA / Q000097:blood / Q000235:genetics; D004249:DNA Damage; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D007962:Leukocytes / Q000378:metabolism / Q000502:physiology; D009154:Mutation; D018384:Oxidative Stress / Q000235:genetics*; D011743:Pyrimidines / Q000378:metabolism*
chemical_list: D011743:Pyrimidines; D004247:DNA
keywords: BRCA mutations; Glycol lesion; Ovarian cancer; Oxidative DNA damage