Title
Exposure-route-dependent DNA adduct formation by polycyclic aromatic hydrocarbons
Author
Godschalk, R.W.L.
Moonen, E.J.C.
Schilderman, A.E.L.
Broekmans, W.M.R.
Kleinjans, J.C.S.
van Schooten, F.J.
Centraal Instituut voor Voedingsonderzoek TNO
Publication year
2000
Abstract
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 delectable 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. Chemicals/CAS: 3-hydroxybenzo(a)pyrene, 13345-21-6; Benzo(a)pyrene, 50-32-8; Benzopyrenes; DNA Adducts
Subject
Nutrition
Benzo[a]pyrene
Polycyclic aromatic hydrocarbon
Animal cell
Animal experiment
Animal model
Animal tissue
Biological monitoring
Controlled study
DNA adduct
DNA binding
Environmental exposure
Leukocyte
Lung parenchyma
Male
Nonhuman
Priority journal
Skin
Urinary excretion
Animals
Benzo(a)pyrene
Benzopyrenes
DNA Adducts
Environmental Exposure
Leukocytes
Male
Rats
Rats, Inbred Lew
Regression
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TNO identifier
58489
ISSN
0143-3334
Source
Carcinogenesis, 21 (1), 87-92
Document type
article