Ornithine decarboxylase induction by chemically complex liquids from two solvent refined coal processes.

Abstract

Studies with a variety of chemically purified substances have suggested that induction of the enzyme ornithine decarboxylase (ODC) in mouse epidermal cells may be a reliable indicator of neoplastic transformation. In an effort to extend these observations on ODC to chemically complex materials, we examined ODC induction by carcinogenic and non-carcinogenic mixtures and compared these results with tumorigenicity data for these materials. For these studies several boiling range fractions and several solvent-derived subfractions from two solvent-refined coal processes (SRC-I and SRC-II) were evaluated for their ability to induce ODC. Single applications of heavy distillate (HD), the SRC-II high-boiling fraction and a potent mouse skin carcinogen, produced ODC induction kinetics which were similar to that for 12-O-tetradecanoylphorbol-13-acetate (TPA). Both HD and TPA stimulated maximal ODC activity 3-5 h after application, with epidermal ODC levels returning to basal levels within 12 h. The magnitude of ODC induction after multiple applications of HD was not as great as that observed for TPA. Single skin applications of TPA and HD also transiently elevated hepatic ODC levels 27- and 7-fold, respectively; however, liver ODC activity did not increase following multiple applications of either chemical. Further, ODC induction by HD was also dose-dependent. Relative to controls, single applications of HD and process solvent (boiling range greater than 250 degrees C) elevated ODC levels 145- to 205-fold, light distillate and light oil (boiling range less than 180 degrees C) increased ODC levels 23- to 32-fold, and middle distillate and wash solvent (boiling range 180-250 degrees C) stimulated less than 2- to 8-fold increases in ODC. Single applications of three solvent-derived subfractions of HD, which are complete carcinogens, induced 3- to 7-fold ODC elevations over background levels; multiple applications of two of these subfractions elevated ODC levels 10- to 22-fold. Of the complex mixtures evaluated during this study, all complete carcinogens induced ODC; however, the magnitude and temporal pattern of induction varied with the material tested.