Studies on the characterization of the genotoxic components of manufactured gas plant residues

Manufactured gas plant (MGP) residues are by-products of coal or oil carbonization processes used for the generation of methane gas. These residues are complex mixtures of a wide variety of organic and inorganic chemicals and trace metals. Studies performed with MGP residues indicate that genotoxic agents, mainly polycyclic aromatic hydrocarbons (PAHs), play an important role in their tumorigenic activity. The present investigation focused on the identification of PAHs responsible for forming DNA adducts in mouse lung, since lung is highly susceptible to tumor formation by MGP residues.; Analytical methods were developed for separation of the various PARDNA adducts formed by complex mixtures. These analytical methods were used to evaluate lung DNA adducts formed by several MGP residues and soils contaminated with residues. Formation of a specific DNA adduct, at relatively higher levels compared to other adducts, was observed with all the samples evaluated. Comparative studies evaluating adducts formed by known genotoxic PAHs failed to identify this adduct. Thus, efforts focused on structural characterization of this unknown adduct.; In vitro systems to generate higher levels of adducts, were investigated in order to facilitate structural elucidation. A chemical fraction of MGP residue obtained by extraction with hexane was instrumental in generating adducts at higher levels. In vitro reactions with individual nucleotides suggested that the unknown adduct is most likely derived from a guanosine base. Species differences in the formation of the unknown adduct were also evaluated with microsomal enzymes isolated from rats, mice, and humans.; Attempts were made to elucidate the structure of the adduct using mass spectral and fluorescence techniques. These efforts were limited due to a high level of interfering compounds. However, sequential fractionation of the MGP residue using HPLC resulted in isolation of a fraction of MGP residue capable of generating the unknown adduct in the in vitro activation system. GC-MS analysis of the isolated fraction indicated the molecular weight of the chemical to be 216.; Significant advances in structural characterization of a highly genotoxic component of MGP residues have been made in these studies. More comprehensive analysis using NMR is necessary to establish exact structure of the chemical.