Carcinogenesis, Vol. 21, No. 1, 87-92,
January 2000
© 2000 Oxford University Press
Carcinogenesis |
Exposure-route-dependent DNA adduct formation by polycyclic aromatic hydrocarbons
Department of Health Risk Analysis and Toxicology, Maastricht University, Universiteitssingel 50, PO Box 616, 6200 MD, Maastricht, The Netherlands
Understanding the kinetics of aromatic–DNA adducts in target tissues and white blood cells (WBC) would enhance the applicability of DNA adducts in WBC as surrogate source of DNA in biomonitoring studies. In the present study, rats were acutely exposed to benzo[a]pyrene (B[a]P; 10 mg/kg body wt) via intratracheal (i.t.), dermal and oral administration. DNA adducts were analyzed in relevant target organs and WBC by nuclease P1 enriched 32P-post-labeling at 1, 2, 4, 11 and 21 days after exposure. Additionally, the internal dose was assessed by measurement of urinary excretion of 3-hydroxy-B[a]P (3-OH-B[a]P). Total B[a]P–DNA adduct levels in WBC were highest after i.t. and oral administration, whereas DNA adducts were hardly detectable after dermal exposure. Highest adduct levels were reached at 2 days after exposure. In lung tissue, DNA adduct levels reached maximal values at 2 days and were highest after i.t., oral and dermal exposure, respectively. DNA adduct levels were significantly lower in WBC as compared with lung. Nonetheless, overall B[a]P–DNA adduct levels in WBC were significantly correlated with those in lung. In target organs, highest DNA adduct levels were observed in skin after topical application, and lowest in stomach after oral administration of B[a]P. Furthermore, DNA adduct levels in WBC were correlated with DNA adduct levels in skin after dermal exposure and stomach after oral administration of B[a]P. Two-fold higher levels of 3-OH-B[a]P were excreted after i.t. administration of B[a]P as compared with dermal or oral exposure. Urinary 3-OH-B[a]P concentrations were correlated with DNA adduct levels at the site of B[a]P application. Overall, it can be concluded that aromatic–DNA adduct levels in WBC can be applied as a surrogate source of DNA for the site of application of B[a]P and reflect binding to lung DNA, independently of the exposure route.
Abbreviations: 3-OH-B[a]P, 3-hydroxy-benzo[a]pyrene; B[a]P, benzo[a]pyrene; i.t., intratracheal instillation; NP1, nuclease P1; PAHs, polycyclic aromatic hydrocarbons; WBC, white blood cells.
1 Present address: Department of Toxicology and Cancer Risk Factors, German Cancer Research Center, PO Box 101949, D-69009 Heidelberg, Germany
2 Present address: Department of Physiology, TNO Voeding, 3700 AJ, Zeist, The Netherlands
3 To whom correspondence should be addressed Email: f.vanschooten{at}grat.unimaas.nl
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