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

Studies with a variety of chemically purified substances havesuggested that induction of the enzyme ornithine decarboxylase(ODC) in mouse epiderinal cells may be a reliable indicatorof neoplastic transformation. In an effort to extend these observationson ODC to chemically complex materials, we examined ODC inductionby carcinogenic and non-carcinogenic mixtures and compared theseresults with tumorigenicity data for these materials. For thesestudies several boiling range fractions and several solvent-derivedsubfractions from two solvent-refined coal processes (SRC-Iand SRC-II) were evaluated for their ability to induce ODC.Single applications of heavy distillate (HD), the SRC-II high-boilingfraction and a potent mouse skin carcinogen, produced ODC inductionkinetics which were similar to that for 12-O-tetradecanoylphorbol-13-acetate(TPA). Both HD and TPA stimulated maximal ODC activity 3–5h after application, with epidermal ODC levels returning tobasal levels within 12 h. The magnitude of ODC induction aftermultiple applications of HD was not as great as that observedfor TPA. Single skin applications of TPA and HD also transientlyelevated hepatic ODC levels 27- and 7-fold, respectively; however,liver ODC activity did not increase following multiple applicationsof either chemical. Further, ODC induction by HD was also dose-dependent.Relative to controls, single applications of HD and processsolvent (boiling range >250°C) elevated ODC levels 145-to 205-fold, light distillate and light oil (boiling range <180°C)increased ODC levels 23- to 32-fold, and middle distillate andwash solvent (boiling range 180– 250°C) stimulated<2- to 8-fold increases in ODC. Single applications of threesolvent-derived subtractions of HD, which are complete carcinogens,induced 3- to 7-fold ODC elevations over background levels;multiple applications of two of these subtractions elevatedODC levels 10- to 22-fold. Of the complex mixtures evaluatedduring this study, all complete carcinogens induced ODC; however,the magnitude and temporal pattern of induction vaned with thematerial tested.