4-Aminobiphenyl (4-ABP)-DNA Damage in Breast Tissue and Relationship to p53 Mutations and Polymorphisms of Metabolizing Genes
Abstract
Only a few epidemiological studies have shown a slight increased risk of breast cancer in cigarette smokers. To evaluate DNA damage due to smoking we studied 4-aminobiphenyl(4-ABP)-DNA adduct levels in breast tumor tissue in a population-based study of 150 cases from New Jersey. All subjects were under the age of 45 with either in situ or invasive breast cancer. Adducts in breast tumor sections of paraffin blocks were measured using an immunohistochemical peroxidase assay. The difference in relative staining intensity for 4-ABP-DNA adducts was not significantly different between smokers, ex-smokers, and non-smokers. Adduct levels was not significantly elevated in smokers with higher compared to lower exposure in relation to age at initiation or pack-years. We then genotyped for enzymes that metabolize 4-ABP; cytochrome P4501A2 (CYPlA2), two N-acetyltransferases, NATl and NAT2, and glutathione-S-transferase(GST). None of these genes, independently or in combination, had a significant association with adduct levels. The p53 mutation spectrum is a useful reporter of past genotoxic exposure. We are currently identifying the mutations for exons 5-8 in the p53 gene with the innovative DHPLC assay. We will correlate the mutation data with smoking status and adduct levels to determine if smoking exposure is a risk for breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2002
- Accession Number
- ADA412857
Entities
People
- Nancy J. Niguidula
- Regina M. Santella
Organizations
- Columbia University