Factors affecting the carcinogenicity of inhaled particle-organic mixtures

An attempt is made to investigate the release of polycyclic aromatic hydrocarbons (PAH) in the lungs following inhalation of particles with adsorbed PAH and the consequences this has for binding of reactive metabolites to cellular macromolecules. DNA adducts are of particular interest because current concepts in chemical carcinogenesis suggest that their formation is an important step in the initiation process. The approach is to use inhalation exposures to single PAH and well-defined particles. The specific hypotheses that are being tested are: (1) A single inhalation exposure to PAH adsorbed on particles will result in slower release of organic compounds, more persistent levels of covalently bound material and greater time-integrated covalent binding of organic compounds, per unit of inhaled PAH, than inhalation of pure compounds. (2) Repeated exposures to inhaled PAH will result in a buildup of DNA adducts to greater time-integrated levels when PAH are adsorbed on particles than when inhaled as pure compounds. (3) Long-term inhalation exposures to PAH-CB will result in greater lung tumor incidence than exposures to pure PAH, correlated with DNA adduct levels. Carbon black particles were selected as carrier particles