Factors affecting possible carcinogenicity of inhaled nitropyrene aerosols

Nitroaromatics in general, and 1-nitropyrene in particular, are potent bacterial mutagens and animal carcinogens. Their importance as possible human carcinogens is difficult to assess because they are usually found in the environment as the products of combustion processes, and so they usually exist with many other compounds associated with airborne particles. The experiments reported here were carried out to determine if the inhalation of particle-associated 1-nitropyrene, or the concomitant exposure to an irritant gas, would alter the tissue distribution of 1-nitropyrene or its metabolites, compared to their distribution after inhalation of pure 1-nitropyrene. These experiments were intended to yield insights into the mechanisms involved in the potential carcinogenicity of particle-associated nitroaromatics as inhaled in the environment from automotive emissions and other sources. Groups of Fischer 344 rats inhaled pure 14C-1-nitropyrene aerosols, with and without coexposure to 5 parts per million sulfur dioxide, or 14C-1-nitropyrene adsorbed onto gallium oxide particles, with and without coexposure to sulfur dioxide, for four weeks. Lung retention of 14C-1-nitropyrene was not prolonged by its association with gallium oxide particles or by coexposure to sulfur dioxide. There was a marked inflammatory and fibrogenic response to the gallium oxide particles. Another set of experiments was carried out in which rats were exposed to 14C-1-nitropyrene either as pure aerosol or adsorbed onto carbon black particles. The amount of 14C in the lung that was bound to carbon black particles steadily decreased with time after exposure, compared to total lung 14C, indicating removal of 14C from the particles. Thirty minutes after exposure, the amount of 14C covalently bound to lung macromolecules, expressed as a percentage of calculated deposited radioactivity, was twofold greater for 1-nitropyrene adsorbed onto carbon black than for 1-nitropyrene alone. The amount of covalently bound 14C increased with time after exposure to 14C-1-nitropyrene adsorbed onto carbon black, reaching a level of approximately 1 percent of deposited radioactivity, 10-fold greater than that seen with pure 14C-1-nitropyrene seven to 30 days after exposure. The level of covalently bound 14C declined steadily after exposure to pure 14C-1-nitropyrene. Carbon black particles associated with adsorbed 1-nitropyrene offer the potential of studying DNA adduct formation in the lung, because DNA modification might be greater after inhalation of 1-nitropyrene adsorbed onto carbon black than after inhalation of pure 1-nitropyrene or 1-nitropyrene associated with metal oxides, such as gallium oxide.(ABSTRACT TRUNCATED AT 400 WORDS)