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Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018
Carcinogen-DNA adducts in human breast epithelial cells
K Gorlewska-Roberts1, B Green, M Fares
1National Center for Toxicological Research, Jefferson, Arkansas 72079, USA.
Environmental and Molecular Mutagenesis
|March 29, 2002
Summary
Exposure to dietary and environmental carcinogens like PhIP, ABP, and B[a]P is confirmed in women. These chemicals form DNA adducts in breast ductal cells, the origin of most breast cancers.
Area of Science:
- Environmental Health
- Molecular Toxicology
- Cancer Etiology
Background:
- Diet and environmental exposures are implicated as significant etiologic factors in human breast cancer.
- Chemicals such as heterocyclic amines, aromatic amines, and polycyclic aromatic hydrocarbons are known mammary carcinogens in animal models.
Purpose of the Study:
- To quantify major DNA adducts from 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 4-aminobiphenyl (ABP), and benzo[a]pyrene (B[a]P) in human breast milk DNA.
- To investigate the presence of these carcinogen-DNA adducts in exfoliated ductal epithelial cells.
Main Methods:
- DNA was isolated from exfoliated ductal epithelial cells in human breast milk from healthy, nonsmoking mothers.
- DNA was digested to 3' nucleotides and subjected to (32)P-postlabeling.
- Adducts were enriched using Oasis Sep-Paks, and analyses were performed by HPLC with radiometric detection, using synthesized bis(phosphate) standards as UV markers.
Main Results:
- Of 64 samples analyzed, 31 contained detectable DNA adducts.
- PhIP adducts were found in 30 samples (mean 4.7 adducts/10(7) nucleotides), ABP adducts in 18 samples (mean 4.7 adducts/10(7) nucleotides), and B[a]P adducts in 13 samples (mean 1.9 adducts/10(7) nucleotides).
- The study successfully synthesized bis(phosphate) standards for critical adducts to aid analysis.
Conclusions:
- Women are exposed to multiple classes of dietary and environmental carcinogens.
- These identified carcinogens react with DNA in breast ductal epithelial cells.
- This DNA adduct formation in breast ductal cells provides insight into breast cancer etiology.
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