title: Bioavailability of benzo(a)pyrene deposited in the lung. Correlation with dissolution from urban air particulates and covalently bound DNA adducts.
abstract: Dissolution kinetics of benzo(a)pyrene (B(a)P associated with urban air particulates were investigated in vitro and related to availability of the carcinogen in the isolated, perfused, and ventilated rat lung. Calculations of bioavailability and mean dissolution time in the lung produced results in concordance with experimental data. By convolution calculation, with in vitro desorption as input function and the disposition of B(a)P dosed intratracheally to the lung in an alveolar surfactant solution as reference, hypothetical areas under B(a)P buffer concentration vs. time curves (AUC) were calculated. AUC value for 1.5 micrograms of microcrystalline (MCr) B(a)P was 16 +/- 2 pmol/ml/min (N = 6), which was identical with the corresponding experimental value of 16 +/- 5 pmol/ml/min (N = 6), from lung perfusion experiments. For B(a)P adsorbed to urban air particulates (UAP-1), predicted and experimental AUC values did amount to 7 +/- 2 (N = 5) and 10 +/- 4 (N = 5) pmol/ml/min, respectively. Absolute bioavailability was calculated by deconvolution to 87% for B(a)P in alveolar surfactant. In vitro dissolution of B(a)P from urban air particulates (UAP-1 to -4) revealed a wide variation in desorption characteristics for different particulate samples. Dissolution parameters determined in vitro were positively related to mean absorption time and mean dissolution time in the lung, using three different preparations. The precision in predictions of availability of B(a)P from in vitro desorption rates, with MCr and UAP-1 representing the greatest differences observed, supports the hypothesis that desorption is the rate-limiting step during uptake of B(a)P in the lung.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medical Nutrition, The Karolinska Institute, Huddinge University Hospital, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Törnquist
authors.forename: M
authors.initials: M
authors.lastname: Nicklasson
authors.forename: P
authors.initials: P
authors.lastname: Söderkvist
authors.forename: L
authors.initials: L
authors.lastname: Nybom
authors.forename: R
authors.initials: R
authors.lastname: Toftgård
mesh_terms: D000395:Air Pollutants, Occupational / Q000032:analysis*; D000818:Animals; D001564:Benzo(a)pyrene / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics*; D001682:Biological Availability; D001711:Biotransformation; D004247:DNA / Q000032:analysis / Q000378:metabolism*; D018736:DNA Adducts; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility
chemical_list: D000395:Air Pollutants, Occupational; D018736:DNA Adducts; C056612:benzo(a)pyrene-DNA adduct; D001564:Benzo(a)pyrene; D004247:DNA