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1.
Toxicol Appl Pharmacol ; 139(2): 430-6, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8806861

ABSTRACT

The disposition and metabolism of 2,3,7,8-tetrachlorodibenzofuran (TCDF) was was investigated in channel catfish (Ictalurus punctatus) in order to better understand the metabolic and physiological factors that modulate the fate of this extremely toxic compound in channel catfish compared to other species. The fish were dosed orally with [3H]TCDF (1 microgram/kg); tissue were harvested at 3, 7, and 14 days for radioassay. The body burden of TCDF equivalents in catfish at 3 days was 0.36 microgram/kg, which was decreasing with a half-life of 3.6 days. Catfish muscle showed a relatively low capacity to accumulate and retain TCDF, accounting, at 3 days, for only 19.0% of the body burden of TCDF equivalents (half-life in muscle, 5.0 days). Catfish liver, on the other hand, showed a high capacity to accumulate and metabolize TCDF and to secrete TCDF metabolites into the bile. At 3 days, the concentrations of TCDF equivalents in liver and bile were, respectively, 5.7 ng/g liver (19% of the body burden) and 129 ng/ml bile. However, the concentration of TCDF equivalents in liver decreased with a half-life of 1.8 days to 0.04 ng/g (2.0% of the body burden) at 14 days. Thus, the capacity of catfish liver to retain TCDF decreased dramatically as the body burden decreased. The data suggest that the low affinity of lipid poor catfish muscle for TCDF may allow catfish liver to accumulate a concentration of TCDF sufficient to induce the metabolism of this compound by liver monooxygenases. The major TCDF metabolites found in catfish liver and bile were, respectively, 4-OH-TCDF and TCDF-4-O-glucuronide.


Subject(s)
Benzofurans/pharmacokinetics , Environmental Pollutants/pharmacokinetics , Ictaluridae/metabolism , Animals , Bile/metabolism , Half-Life , Liver/metabolism , Tissue Distribution
2.
Toxicol Appl Pharmacol ; 130(2): 188-96, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7871532

ABSTRACT

The metabolism of 2-acetyl-[9-14C]aminofluorene (AAF) by hepatocytes isolated from rainbow trout (Oncorhynchus mykiss), Shasta strain, was investigated in order to assess the competing activation and detoxification pathways which may explain the resistance of this species and strain to the initiation of carcinogenesis by this model carcinogenic aromatic amide. Freshly isolated hepatocytes (per milliliter: 1.0 mg dry wt; 1.5 (10(6)) hepatocytes) incubated with 65 microM AAF for 4 hr converted 15.4 nmol AAF to metabolites, including 7.8 nmol of water-soluble compounds. AAF-derived radioactivity extracted from the incubation mixtures, before and after hydrolysis by beta-glucuronidase and arylsulfatase, was analyzed by reversed-phase HPLC. The metabolite profile following incubation of hepatocytes with 6.5 microM AAF for 4 hr included (as percentage of total metabolites); 7-OH-AAF, 5-/8-/9-OH-AAF and 2-aminofluorene (AF) (17, 2.4, and 2.7%, respectively); conjugates of these respective primary metabolites (39, 9, and 4%, respectively). Glucuronides amounted to 49% of the total metabolites. N-OH-AAF and its conjugates always amounted to < 1% of total metabolites. The relative amount of (unconjugated) AF increased considerably (to 26%) following incubation of hepatocytes with 65 microM AAF, with a corresponding decrease in the total amount of glucuronides formed. Following incubation with 65 microM AAF, 1.6% of AAF metabolites was covalently bound to macromolecules, giving a ratio of covalently bound derivatives to detoxification products of 0.028. These data are consistent with the hypothesis that rainbow trout are resistant to AAF-induced hepatocarcinogenesis, in part, because trout liver efficiently detoxifies AAF and forms only relatively small amounts of active intermediates capable of binding to macromolecules, including DNA.


Subject(s)
2-Acetylaminofluorene/metabolism , Liver/metabolism , Animals , Chromatography, High Pressure Liquid , In Vitro Techniques , Oncorhynchus mykiss
3.
Oral Surg Oral Med Oral Pathol ; 72(1): 101-4, 1991 Jul.
Article in English | MEDLINE | ID: mdl-1891227

ABSTRACT

The antimicrobial effectiveness of calcium hydroxide, camphorated paramonochlorophenol, and formocresol in root canals of extracted human teeth was compared. Canals in single-rooted teeth were enlarged and inoculated with Streptococcus mutans, Actinomyces viscosus, and Bacteroides gingivalis or Bacteroides fragilis. After treatment with a test agent and sealing and incubation for 1 hour, the canal contents were analyzed for the number of viable test bacteria and compared with that of inoculated teeth not treated with test agents. All test agents exhibited antimicrobial activity against all bacteria, with percent reductions in viable bacteria ranging from 64.3% to 100%. The combined data for Pulpdent paste and calcium hydroxide showed significantly higher antimicrobial activity than the combined data for camphorated paramonochlorophenol and formocresol for S. mutans and B. gingivalis or B. fragilis but showed no difference for A. viscosus.


Subject(s)
Actinomyces/drug effects , Anti-Infective Agents, Local/pharmacology , Bacteroides/drug effects , Calcium Hydroxide/pharmacology , Camphor/pharmacology , Chlorophenols/pharmacology , Formocresols/pharmacology , Streptococcus mutans/drug effects , Adult , Colony Count, Microbial , Dental Pulp Capping , Dental Pulp Cavity/microbiology , Drug Combinations , Humans , Materials Testing
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