Acute toxicity of four drinking water disinfection by-products to Japanese medaka fish.
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Animals↗
Biomedical subjects
M W Toussaint
Publications and source records attributed to M W Toussaint.
Chronic toxicity of chloroform to Japanese medaka fish.
Japanese medaka (Oryzias latipes) were continually exposed in a flow-through diluter system for 9 months to measured chloroform concentrations of 0.017, 0.151, or 1.463 mg/L. Parameters evaluated were hepatocarcinogenicity, hepatocellular proliferation, hematology, and intrahepatic chloroform concentration. Histopathology was evaluated at 6 and 9 months. Chloroform was not hepatocarcinogenic to the medaka at the concentrations tested. Chronic toxicity was evidenced at these time points by statistically significant ([alpha] = 0.05) levels of gallbladder lesions and bile duct abnormalities in medaka treated with 1.463 mg/L chloroform. We assessed hepatocellular proliferation by exposing test fish to 5-bromo-2'-deoxyuridine in the aquarium water for 72 hr after 4 and 20 days of chloroform exposure; we then quantified area-labeling indices of the livers using computer-assisted image analysis. We observed no treatment-related increases in cellular proliferation. We analyzed cells in circulating blood in medaka after 6 months of chloroform exposure. Hematocrit, leukocrit, cell viability, and cell counts of treated fish were not significantly different from those of control fish. Using gas chromatography (GC), we evaluated intrahepatic concentrations of chloroform in fish after 9 months of exposure. Livers from the 0.151 and 1.463 mg/L chloroform-treated fish had detectable amounts of chloroform, but these levels were always lower than the aquaria concentrations of chloroform. Thus, it appeared that chloroform did not bioaccumulate in the liver. Unidentified presumptive metabolite peaks were found in the GC tracings of these fish livers.
Animals↗
Environmental complex mixture toxicity assessment.
Trichloroethylene (TCE) was found as a contaminant in the well supplying water to an aquatic testing laboratory. The groundwater was routinely screened by a commercial laboratory for volatile and semivolatile compounds, metals, herbicides, pesticides, and polychlorinated biphenyls using U.S. Environmental Protection Agency methods. Although TCE was the only reportable peak on the gas chromatograph, with average concentrations of 0.200 mg/l, other small peaks were also present, indicating the possibility that the contamination was not limited to TCE alone. A chronic 6-month carcinogenicity assay was conducted on-site in a biomonitoring trailer, using the Japanese medaka fish (Oryzias latipes) in an initiation-promotion protocol, with diethylnitrosamine (DEN) as the initiator and the TCE-contaminated groundwater as a promoter. Study results indicated no evidence of carcinogenic potential of the groundwater without initiation. There was, however, a tumor-promotional effect of the groundwater after DEN initiation. A follow-up laboratory study was conducted using reagent grade TCE added to carbon-filtered groundwater to simulate TCE concentrations comparable to those found in the contaminated groundwater. Study results indicated no promotional effects of TCE. These studies emphasize the necessity for on-site bioassays to assess potential environmental hazards. In this instance, chemical analysis of the groundwater identified TCE as the only reportable contaminant, but other compounds present below reportable limits were noted and may have had a synergistic effect on tumor promotion observed with the groundwater exposure. Laboratory toxicity testing of single compounds can produce toxicity data specific to that compound for that species but cannot take into account the possible toxic effects of mixtures of compounds.
Adenoma, Liver Cell↗
Maggiemycin and anhydromaggiemycin: two novel anthracyclinone antitumor antibiotics. Isolation, structures, partial synthesis and biological properties.
Two new anthracyclinone antitumor antibiotics, maggiemycin (6, NSC-D344012) and anhydromaggiemycin (8) have been isolated from a culture of an unspeciated Streptomyces (ATCC No. 39235). Bioautography against Bacillus subtilis was used for the preliminary detection of these anthracyclinones. Structures were proposed based on their UV-visible, IR, 1H NMR, 13C NMR spectra, electron impact (EI) and high-resolution EI-MS and confirmed by partial synthesis and a direct correlation with epsilon-rhodomycinone. Both the anthracyclinones are active against KB, P388 and L1210 murine tumor cell lines; however, anhydromaggiemycin was more active than maggiemycin. A number of related anthracyclinones have also been prepared and their biological activity has been determined. The structure-activity relationship of these new anthracyclinones is also discussed.
Animals↗
Fredericamycin A, a new antitumor antibiotic. I. Production, isolation and physicochemical properties.
A new antitumor antibiotic, fredericamycin A (FCRC-A48, NSC-305263), has been isolated from a strain of Streptomyces griseus (FCRC-48). Based on its unique ultraviolet-visible spectrum, infrared spectrum, proton and carbon-13 nuclear magnetic resonance spectra and mass spectra, it is judged to be a novel acid-base indicator type of compound. Its production, isolation and physicochemical properties are discussed. The isolation, ultraviolet-visible spectrum and some biological properties of two minor components, fredericamycin B and fredericamycin C, are also described.
Antibiotics, Antineoplastic↗
High-performance liquid chromatography and thin-layer chromatography of anthracycline antibiotics: separation and identification of components of the dauno-rubicin complex from fermentation broth.
A new solvent system composed of methanol-acidic water (pH 2.0 with phosphoric acid) has been developed for high-performance liquid chromatography of the daunorubicin complex from fermentation broth on a micro Bondapak C18 column. Application of this solvent system in conjunction with thin-layer chromatography in the identification of anthracycline antibiotics from the fermentation broth is discussed.
Chromatography, High Pressure Liquid↗
An in vivo method for using 5-bromo-2'-deoxyuridine (BrdU) as a marker of chemically-induced hepatocellular proliferation in the Japanese medaka (Oryzias latipes).
Japanese medaka fish (Oryzias latipes) were used to develop an in vivo method to assess hepatocellular proliferation in a nonmammalian model. Proliferative responses were assessed in medaka at 7, 17, 24, and 94 days after a 48-hour exposure to 10 or 100 mg/L diethylnitrosamine (DEN). Subgroups of medaka were exposed to 50 or 75 mg/L of 5-bromo-2'-deoxyuridine (BrdU) in water for 72 hours, sacrificed, and then processed for immunohistochemical staining. Proliferative indices of BrdU-labeled hepatocytes were quantified and compared using both count and area measurements. There was a significant increase (p < 0.05) in hepatocellular proliferation in the 100 mg/L DEN-treated fish as compared to controls and 10 mg/L DEN-treated fish for the first 3 time points. Hepatocarcinogenicity was evaluated 26 weeks post-DEN exposure. There was a significant increase (p < 0.0001) in hepatocellular neoplasms in 100 mg/L DEN-treated fish compared to other fish. Effective BrdU-labeling of S-phase hepatocytes in medaka was achieved by adding BrdU to the aquarium water, and an increase in hepatocellular proliferation using this method was detected 7 days after exposure to a carcinogenic concentration of DEN. Additionally, the new method of area measurement indices of proliferation were as precise as count indices (R2 > or = 0.92).
Adenoma, Liver Cell↗
Chronic toxicity of bromodichloromethane to the Japanese medaka (Oryzias latipes).
Japanese medaka (Oryzias latipes) were continually exposed in a flow-through diluter system for 9 months to measured bromodichloromethane (BDCM) concentrations of 0.018, 0.143, or 1.424 mg/L. Parameters evaluated were hepatocarcinogenicity, hepatocellular proliferation, hematology, and intrahepatic BDCM concentration. BDCM was not hepatocarcinogenic to medaka at the concentrations tested. Chronic toxicity was evidenced at 6 and 9 months by statistically significant (alpha = 0.05) levels of gallbladder lesions and bile duct abnormalities in medaka treated with 1.424 mg/L BDCM. Hepatocellular proliferation was assessed after 1, 4, and 20 days of BDCM exposure. Treatment-related increases or decreases in cellular proliferation were not observed at any time point. Hematocrit, leukocrit, cell viability, and cell counts of treated fish after 9 months of BDCM exposure were not significantly different from control fish. Intrahepatic concentrations were evaluated by gas chromatography after 9 months of BDCM exposure. Fish livers from all three BDCM treatments had detectable amounts of BDCM, with median intrahepatic concentrations of 1.02, 2.89, and 21.25 mg BDCM/kg fish liver in the low, middle, and high concentrations, respectively. Medaka chronic toxicity effects of statistically significant gallbladder and bile duct abnormalities occurred at 1.424 mg/L BDCM, well above median drinking water levels.
Animals↗
Histopathology of Japanese medaka (Oryzias latipes) chronically exposed to a complex environmental mixture.
Japanese medaka (Oryzias latipes) were used to evaluate the carcinogenicity of a complex groundwater that contained 5 U.S. Environmental Protection Agency priority pollutant heavy metals and 13 chlorinated aliphatic hydrocarbons. A test protocol that used 10 mg/L diethylnitrosamine (DEN) prior to groundwater exposure was designed to assess both initiation and promotion. The fish were exposed continuously for 9 mo with 0, 1, 5, or 25% groundwater, by volume, with either West Branch of Canal Creek water (Aberdeen Proving Ground-Edgewood Area, Aberdeen Proving Ground, MD) or dechlorinated tap water as the diluent, while concurrent controls were run in the laboratory. Incidental findings included various neoplasms in the nares, ovary, skeletal muscle, skin, swim bladder, testis, thymus, and thyroid. Factors evaluated during statistical analyses of fish neoplasm prevalence included diluent type, groundwater percentage, fish gender, and DEN initiation. Liver neoplasm prevalence was higher in DEN-initiated fish and was frequently higher in males. Concentrations of up to 25% groundwater, by volume, showed no evidence of being a complete carcinogen and showed no consistent, conclusive evidence of being a promoter.
Adenoma↗