Carcinogenesis, Vol. 22, No. 5, 741-749,
May 2001
© 2001 Oxford University Press
CARCINOGENESIS |
The rapid alveolar absorption of diesel soot-adsorbed benzo[a]pyrene: bioavailability, metabolism and dosimetry of an inhaled particle-borne carcinogen
Institute of Environmental Medicine, Division of Inhalation Toxicology, Karolinska Institutet, Box 210, SE-171 77 Stockholm, Sweden and National Institute for Working Life, Solna, Sweden,
1 Lovelace Respiratory Research Institute, PO Box 5890, Albuquerque, NM 87185, USA and
2 Battelle Memorial Institute, 505 King Avenue, Columbus, OH 43201-26, USA
Exposure to diesel exhaust may contribute to lung cancer in humans. It remains unclear whether the carbonaceous core of the soot particle or its coat of adsorbed/condensed organics contributes most to cancer risk. Equally unclear are the extent and rate at which organic procarcinogens desorb from soot particles in the lungs following inhalation exposure and the extent of their metabolic activation in the lungs. To explore the basic relationship between a model polycyclic aromatic hydrocarbon (PAH) and a typical carrier particle, we investigated the rate and extent of release and metabolic fate of benzo[a]pyrene (BaP) adsorbed on the carbonaceous core of diesel soot. The native organic content of the soot had been denuded by toluene extraction. Exogenous BaP was adsorbed onto the denuded soot as a surface coating corresponding to 25% of a monomolecular layer. Dogs were exposed by inhalation to an aerosol bolus of the soot-adsorbed BaP. Following deposition in the alveolar region a fraction of BaP was rapidly desorbed from the soot and quickly absorbed into the circulation. Release rates then decreased drastically. When coatings reached ~16% of a monolayer the remaining BaP was not bioavailable and was retained on the particles after 5.6 months in the lung. However, the bioavailability of particles transported to the lymph nodes was markedly higher; after 5.6 months the surface coating of BaP was reduced to 10%. BaP that remained adsorbed on the soot surface after this period was ~30% parent compound. In contrast, the rapidly released pulse of BaP, which was quickly absorbed through the alveolar epithelium after inhalation, appeared mostly unmetabolized in the circulation, along with low concentrations of phase I and phase II BaP metabolites. However, within ~1 h this rapidly absorbed fraction of BaP was systemically metabolized into mostly conjugated phase II metabolites. The results indicate that absorption through the alveolar epithelium is an important route of entry to the circulation of unmetabolized PAHs.
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