Particle-associated polycyclic aromatic hydrocarbons--a reappraisal of their possible role in pulmonary carcinogenesis.
According to the model presented here, large aggregates of inert dust forming in the lung can drastically increase retention of polycyclic aromatic hydrocarbons (PAHs) that are either adsorbed or precipitated onto the dust particles. Experiments designed to demonstrate the carcinogenicity of PAHs in animals require that large amounts of PAHs be administered to induce lung cancer. If the PAHs are attached to an inert carrier dust before instillation, aggregation of particles is a very significant factor in the retention of PAHs in the lung. A slow release of particle-associated PAHs would result in a prolonged exposure to surrounding tissues from a limited number of administrations. Because an increased incidence of tumors has been observed following these types of exposures, it has been concluded that the increased retention of PAHs due to their association with inert particles is an important factor in PAH-induced pulmonary carcinogenesis. However, large aggregates of inert dust containing crystalline PAHs are unlikely to form with the much lower doses typical of human exposures. Inhaled particles are more likely to deposit and react with the surrounding lung medium without interference from other particles. Our model demonstrates that, under more typical, low-dose exposure conditions, particle-associated PAHs will be released rapidly from the particles. Sustained exposure of target tissues to PAHs will result from repeated exposures, not from increased retention due to association of PAHs with their carrier particles. This distinction is very important, because in high-dose, instillation experiments in animals, critical doses to cells, and thus tumors, should occur at the sites at which particles are retained; whereas, the much lower, but more frequent exposures common for humans should instead lead to tumors at the sites at which particles are initially deposited, but not necessarily retained.
Gerde
P
P
Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico 87185.
Medinsky
M A
MA
Bond
J A
JA
D000818:Animals; D004391:Dust / Q000009:adverse effects; D008175:Lung Neoplasms / Q000139:chemically induced*; D008954:Models, Biological; D010316:Particle Size; D011083:Polycyclic Compounds / Q000493:pharmacokinetics / Q000633:toxicity*
D004391:Dust; D011083:Polycyclic Compounds