Journal of environmental pathology and toxicology最新文献

The mutagenic potential of povidone-iodine (PVP-I) and some related compounds were studied using the L5178Y mouse (TK+/-) lymphoma assay. The established mutagens ethyl methanesulfonate (EMS) and dimethylnitrosamine (DMN) were highly active in this assay, whereas PVP-I, polyvinyl pyrolidone (PVP), potassium iodide (KI), and iodine (I2) were inactive. Furthermore, in the presence of a rat liver microsomal activating fraction (S-9), PVP-I and I2 had only marginal activity as mutagens. Using the Balb/c 3T3 transformation assay we assessed the transformational capacities of these same agents and the positive mutagen N-methyl-N-nitro-N-nitrosoguanidine (MNNG). All concentrations of the compounds tested were inactive in this assay except for PVP-I (5 mg/ml) and MNNG (5 micrograms/ml). However, the response with PVP-I was only marginal. We concluded from these studies that PVP, PVP-I, KI, and I2 did not possess any biologically significant mutagenic or cell transforming ability.

Young adult male cats were exposed 28 days, 20 hrs per day, to a 1:14 dilution of diesel exhaust emissions. Following termination of exposure, the following pulmonary function measurements were carried out: lung volumes, maximum expiratory flow rates (MEF), MEF at 50%, 25% and 10% of vital capacity (VC): forced expiratory volume (FEV) after 0.2, 0.3 and 0.4 sec, dynamic compliance, resistance and helium washout at 25, 50, 75, and 100 breaths per min. The only significant functional change was a decrease in MEF at 10% of VC (P x .02). The lungs of the exposed cats appeared charcoal grey with frequent focal black spots visible on the pleural surface. Pathologic changes in the exposed cats included a predominantly peribronchiolar localization of black-pigmented macrophages within the alveoli producing a focal pneumonitis or alveolitis. In general, evidence of serious lung damage was not observed following the 28-day exposure period.

Rats were subjected to stress by isolation for periods of up to eight days, which produced an elevation in plasma cortisol. In vivo drug metabolism as estimated by the plasma elimination rate of orally-administered antipyrine was not significantly affected by this treatment although there was an apparent decrease in the absorption rate of the drug. In vitro experiments on hepatic microsomal preparations derived from stressed animals indicate that this stress increased in the activity of some enzyme systems concerned with benzo(a)pyrene activation and this correlated with an increased binding of the carcinogen to DNA. The activity of conjugating enzyme which could catalyze the excretion of such carcinogens was not significantly altered. The results indicated that stress could have an important bearing on carcinogenesis by enhancing to a greater extent enzyme systems responsible for activation than those involved in the excretion of polycyclic aromatic hydrocarbons.

Fetotoxicity of di-(2-ethylhexyl)phthalate (DEHP) and its metabolite, mono-(2-ethyhexyl)phthalate (MEHP) was studied in pregnant mice (ddY-Slc female X CBA male). With the oral administration of DEHP 5.0 or 10.0 ml/kg representing 1/6 or 1/3 of the acute LD50 dose on day 7 of gestation there were no live fetuses. When DEHP 10.0 ml/kg was given on days 9 or 10 of gestation, however, the rates of live fetuses were 91.7% and 95.4% respectively. Gross and skeletal abnormalities in the live fetuses occurred with 2.5 or 7.5 ml/kg of DEHP given orally on days 7 or 8 of gestation respectively. Similar toxic effects were observed with the administration of MEHP. The oral administration of 0.5 or 1.0 mg/kg on day 8 of gestation resulted in 11-19% and 100% of gross and skeltal abnormalities, respectively. The gross abnormalities included exencephaly, open eyelid and club foot. Skeltal abnormalities occurred in the skull, cervical and/or thoracic bones. Thus both DEHP and MEHP exert similar effects on the mouse fetus and the lethal and/or teratogenic effects of DEHP are probably due to its metabolite, MEHP.

A method is presented for producing silicone rubber replica casts of the entire respiratory airways (nasal cavity, pharyngeal region, and lungs) for toxicological assessment of inhaled particles and gases. Established methods for producing casts of the lungs are combined with other methods for faithful casting of the nasopharyngeal region to simultaneously cast all the respiratory regions of a given animal. The resulting detailed, flexible casts can be examined for comparison of the features and relative positions of the regions of the respiratory tracts of various animal species.

As shown previously, newly synthesized DNA from Chinese hamster, excision proficient and excision deficient xeroderma pigmentosum (XP) cells treated with split doses of N-acetoxy-acetylaminofluorene (AAAF) or ultraviolet radiation (uv) is larger in size than DNA from cells treated with only the single dose. In this report we determined the effects of caffeine, an inhibitor of postreplication repair, upon enhancement of repair by a split dose treatment with AAAF. Caffeine was added to cells either immediately following the first or the second dose of AAAF and the size of newly synthesized DNA was determined by alkaline sucrose gradient sedimentation. Results showed that: (a) the DNA from V79 and XP cells incubated with caffeine between the first and second dose of AAAF was smaller in size than DNA from cells not incubated with caffeine; (b) caffeine exhibited a lesser effect when added after the second dose during the pulse-chase; and (c) caffeine has little effect upon daughter DNA of normal human cells treated with single or split doses of AAAF. These data indicate that caffeine interferes with the enhancement of postreplication repair in V79 and XP cells treated with AAAF.

The In Vitro information System (IVIS) provides for the collection, maintenance, analysis and reporting of mutagenesis data for the In Vitro Carcinogenesis Program of the Carcinogenesis Testing Program in the National Cancer Institute. Initial development or IVIS focused on the microbial mutagenicity assays conducted in a collaborative study in four laboratories. Information is collected about contract management, chemicals, microorganisms strain checks, preparation of activation enzymes, test results, and confirmation of mutation. IVIS provides for editing and maintenance of the information on computers at the National Institutes of Health. Analysis and reporting features were designed to assist both laboratory investigators and NCI staff in evaluating the mutagenic activity of test compounds. The analysis has focused on two principal goals: using the computer to examine the results of each test to determine if the test was adequate for a further statistical analysis; and secondly, if the plate counts are adequate, developing statistics that indicate whether there is a positive or negative trend. Reports have been developed for tabular displays of test results, frequency distributions, dose response graphs and statistical computations.

In this investigation of the effects of diphenylguanidine (DPG) on pregnancy and fetuses, pregnant mice of the ICR-JCL strain were given dPG orally in a 0.5 percent carboxymethyl cellulose suspension in doses of 0.25, 1.0, 4.0, or 10.0 mg/kg of body weight/day throughout pregnancy. Control mice were fed the vehicle alone. On day 18 of pregnancy, all mice were killed and the fetuses were examined. Disturbances in implantation were seen in the mothers treated with 10 mg/kg/day (the highest dose) of DPG. Retarded ossification of the talus was seen in the fetuses of mothers treated with 4.0 mg/kg/day, but there was no dose-response relationship to this finding. Although malformations such as open eyelids or polydactyly were seen sporadically, these were categorized as spontaneous anomalies. Thus, DPG seems to have no detrimental effects on the development of mouse fetuses in doses of 4 mg/kg or less.

A study has been made of the effects of lead on developing muscle using a cell culture system. When the L6 clonal cell line was treated with lead acetate in culture during the first or second day after plating (but not at later times) fusion of cells to form skeletal muscle straps was inhibited. This inhibition was not due to a general toxic effect of lead on the cells since cell division continued at a normal rate during the first 10 days of culture after lead addition. When cells were examined ultrastructurally using stereology, the only apparent effect of lead was a change in mitochondrial size and configuration. Five times as many partially condensed mitochondria were seen in lead treated cells, and mitochondrial size was also significantly increased. Lead appears to effect a very early event in cell fusion since gap junction formation (a necessary event in fusion) and some synthesis of myofibrils occur even in the presence of lead.