Pyrimidine base damage is increased in women with BRCA mutations

• Published in: Cancer letters 2013-09, Vol.338 (2), p.267-270
• Main Authors: Budzinski, Edwin E, Patrzyc, Helen B, Dawidzik, Jean B, Freund, Harold G, Frederick, Peter, Godoy, Heidi E, Voian, Nicoleta C, Odunsi, Kunle, Box, Harold C
• Format: Article
• Language: English
• Subjects: animal ovaries; Antioxidants; BRCA mutations; Breast cancer; Case-Control Studies; DNA; DNA - blood; DNA - genetics; DNA Damage; DNA repair; experimental design; Female; Genes; Genes, BRCA1; Genes, BRCA2; Genetic Predisposition to Disease; Glycol lesion; Hematology, Oncology and Palliative Medicine; Humans; Leukocytes - metabolism; Leukocytes - physiology; Mutation; Ovarian cancer; ovarian neoplasms; Oxidative DNA damage; oxidative stress; Oxidative Stress - genetics; Pyrimidines - metabolism; thymine; women
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2013.04.001

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.