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Exposure-route-dependent DNA adduct formation by polycyclic aromatic hydrocarbons
R W Godschalk1, E J Moonen, P A Schilderman
1Department of Health Risk Analysis and Toxicology, Maastricht University, Universiteitssingel 50, PO Box 616, 6200 MD, Maastricht, The Netherlands.
Carcinogenesis
|December 23, 1999
Summary
Benzo[a]pyrene (B[a]P) DNA adducts in white blood cells (WBC) can serve as a reliable indicator for exposure in target tissues. Adduct levels in WBC correlate with lung and application site DNA, regardless of exposure route.
Area of Science:
- Environmental Toxicology
- Biomonitoring
- Chemical Carcinogenesis
Background:
- Aromatic-DNA adducts are biomarkers of exposure to carcinogens like benzo[a]pyrene (B[a]P).
- Understanding the kinetics of B[a]P-DNA adducts in white blood cells (WBC) is crucial for their use as surrogates in biomonitoring.
Purpose of the Study:
- To investigate the time-course and tissue-specific kinetics of B[a]P-DNA adducts following different administration routes in rats.
- To evaluate the utility of WBC DNA adducts as surrogates for target tissue DNA adducts.
Main Methods:
- Rats were exposed to B[a]P via intratracheal, dermal, or oral routes.
- B[a]P-DNA adducts were quantified in target organs and WBC using (32)P-post-labeling.
- Urinary 3-hydroxy-B[a]P (3-OH-B[a]P) was measured to assess internal dose.
Main Results:
- WBC B[a]P-DNA adduct levels peaked at 2 days post-exposure and were highest after intratracheal and oral routes.
- Adduct levels in WBC were significantly lower than in lung tissue but showed significant correlations with lung adducts.
- Urinary 3-OH-B[a]P correlated with DNA adducts at the site of B[a]P application.
Conclusions:
- WBC DNA adducts serve as a valid surrogate for B[a]P exposure, reflecting binding in lung tissue irrespective of the administration route.
- The findings support the use of WBC DNA adducts in biomonitoring studies for aromatic hydrocarbon exposure.