Journal of environmental pathology and toxicology最新文献

The model of hepatic regeneration is chosen to study the effect of methylmercury burden on cell proliferation. The results show that chronic methylmercury burden impedes the rate of thymidine incorporation during the process of DNA synthesis. At 24 hours after partial hepatectomy, thymidine incorporation in the mercury exposed rats is 53% of the controls. Counts of labeled hepatocytes in radioautographic preparations also support this observation. This remarkable difference in DNA synthetic activity at 24 hours also reflects in the DNA content and liver, weights at 72 hours after partial hepatectomy (Liver weights 2.36 +/- 0.21 gm/100 gm B. W. vs. 2.67 +/- 0.31 gm/100 B. W., P < 0,05; DNA contents 160.78 +/- 36.76 microgram/gm vs. 214.80 +/- 37.908 microgram/gm, P < 0.05). After two weeks, no significant difference is noted in liver weight, DNA content and synthetic activity. On the other hand, protein content and biosynthesis in the liver of methylmercury burdened rats shows no significant difference from the controls in all the periods studied. From these data it is concluded that the dividing fraction of hepatocytes is reduced in methylmercury-treated group at an early stage of regeneration when cell proliferation is most active.

Calculi in the urinary tract is a disease which afflicts not only man, but also experimental animals. The incidence of human stone disease varies widely according to the geographical area. With the advent of sophisticated physicochemical techniques, the elucidation of structure and the quantification of mineral components of urinary calculi have been greatly facilitated. In addition to calcium oxalate and calcium phosphate, more than ten other minerals and a large number of trace elements have been identified to date. Matrix material consists of such macro-molecules as proteins and mucopolysaccharides. The etiology of urinary calculi is varied; diet, drugs, chemicals, bladder implants, infections, metabolic derangements, and environmental influences are some of the factors that can contribute to the pathogenesis of stones. The literature findings reflect the complexity of urolithiasis as a clinicopathological problem.

The effects of chlordecone and mirex on the rat myocardial ATPases and binding of 3H-dopamine and 3H-norepinephrine to the NAK-fraction were determined both by in vitro and in vivo treatment. The in vitro data showed that chlordecone significantly inhibited mitochondrial Mg2+ ATPase and Na+--K+ ATPase in a concentration dependent manner with ID50 values of 5 x 10(-8) and 2 x 10(-6) M, respectively. Mitrex, a close structural analog of chlordecone did not inhibit mitochondrial Mg2+ ATPase but inhibited about 15% of N+--K+ ATPase activity. Rats treated with symptomatogenic doses of chlordecone showed a marked and significant decrease of myocardial Na+--K+ ATPase and the residual Mg2+ ATPase activities. The decrease in the enzyme activities was dose dependent and significant. However, mirex treated rats showed a slight decrease in the myocardial Na+--K+ ATPase. The potency of chlordecone to inhibit the ATPase system was parallel to its ability to decrease the dopamine and norepinephrine binding of the myocardial NAK-fraction. Preincubation of the NAK-fraction with various concentrations of chlordecone resulted in a decreased binding of dopamine and norepinephrine. The decrease was significant and concentration dependent. Similar findings were observed in rats pretreated with chlordecone. Mirex did not show any effect, either in vitro or in vivo treatment, on the binding of dopamine or norepinephrine to the myocardial NAK-fraction. These results suggest that chlordecone may be altering the sodium pump activity by inhibiting both ATP hydrolysis and ATP synthesis and thus reducing other cellular events such as catecholamine uptake.

The carcinogenicity of sodium benzoate was examined in Fischer 344 rats. Sodium benzoate was administered in the diet for 18 to 24 months at two dose levels; concentrations of 2% and 1% in the diet, which corresponded to the maximum tolerated dose (MTD) and 1/2 MTD as estimated from the data obtained by 6-week toxicity study. Fifty males and 52 females each were used per group. Controls consisted of 25 male rats and 43 female rats. No adverse clinical signs directly attributable to the compound were observed in treated animals. Differences in the average body weight, and mortality rates between treated and control groups were negligible. The results of the statistical test for dose-related trends were not significant (p < 0.05) Although a variety of tumors occurred among test and control rats of each sex, tumors appearing in treated rats were similar in type and number to those in controls. It was concluded that no evidence of carcinogenicity in rats from sodium benzoate was demonstrated.

The comparative carcinogenicity of dimethylcarbamoyl chloride (DMCC) was studies in male, Syrian Golden Hamsters by inhalation. Hamsters were exposed to 1ppm and the exposure periods were 6 hours per day, 5 days per week for the lifetime of the animals. Fifty-one percent of the hamsters developed carcinomas of the nasal tract. Morphologically, all of these tumors were classified as squamous cell carcinomas. In comparing the response of rats and hamsters at 1 ppm DMCC, the rat seems to show increased sensitivity and the percentage of tumor yield is almost doubled, with the tumors appearing much earlier in rats than in hamsters. However, the remarkable tumor yield in both species indicates the potent carcinogenic effects of DMCC.

Swiss/ICR mice were tested to determine whether the volatile ether anesthetic, enflurane, causes induction of anesthetic defluorination and organ toxicity. Mice were exposed in utero and postnatally to 0.01, 0.1 and 1.0 volumes percent enflurane vapor. Body weight was measured at frequent intervals throughout the experiment. Animals were sacrificed at 73 days of age and liver microsomal cytochrome P-450 content and the rate of defluorination of enflurane, isoflurane, methoxyflurane ans sevoflurane were determined. In addition, the liver, kidney and testis were weighed and examined histologically for drug induced damage. The maximum tolerated dose of enflurane delivered over a twelve week period was determined to be 0.5 volumes percent for four hours a day, five days a week. Even at this high dose there was no evidence in either sex of liver, kidney or testicular damage. Following enflurane exposure, neither the liver microsomal cytochrome P-450 content nor the rate of anesthetic defluorination was increased. The rate of in vitro inorganic fluoride production per unit time was greatest for methoxyflurane, and approximately equal for enflurane, isoflurane and sevoflurane. Since there was no evidence of enzyme induction or specific organ toxicity, it was concluded that enflurane is a comparatively nontoxic volatile anesthetic under conditions of this study.

The carcinogenicity of the nitrosourea amino acid, N delta-(N-methyl-N-nitrosocarbamoyl)-L-ornithine (MNCO), and its acute cytotoxicity were studied in Wistar rats. MNCO treatment induced a high incidence of neoplasms in breast, kidney, and skin and a lower incidence of tumors in the exocrine pancreas and ear duct. The duration of these studies was limited by toxicity and carcinogenicity to six months in a high dose group which received 1 mmole MNCO/kg IP weekly for 6 months and to 1 year in a group which received 0.33 mmole/kg. In the latter group the incidence of neoplasms was breast, 40%; skin, 52%; kidney, 81%; pancreas, 19%; and ear duct, 4%. All pancreases in this group also contained foci of fibrosis and cyst formation, and atypical acinar cell nodules. Acute cytotoxic effects were noted in pancreas, kidney and skin after a single IP injection of 3 mmoles/kg although this dose caused no deaths acutely.

This study was undertaken to evaluate the mutagenicity of the flame retardant, Tetrakis (Hydroxymethyl) Phosphonium Sulfate -75% or its possible metabolic products using a battery of in vitro and in vivo assays. The starting material in the fabric treatment process, THPS was tested with five strains of Salmonella typhimurium with and without the addition of a rat liver activating system. In addition, the THPS and the treated fabric were assayed in a combined testing protocol. The mutagenicity tests which were employed in this protocol included (a) the analysis of the urine of treated mice, (b) the micronucleus test, and (c) metaphase analysis. The animals were administered the THPS both orally and dermally and the treated fabric was incorporated into the animals' feed. The THPS produced no mutagenic response in any of the strains of S. typhimurium either when tested directly or with the addition of Acroclor--or phenobarbital-- induced rat liver. The results of the combined testing protocol, with the three routes of administration, were also negative for the urine analysis, micronucleus test and metaphase analysis.

Epidermoid metaplasia, of a type that consistently progresses to epidermoid carcinoma, was induced in rats at the interface of pulmonary tissue and intrapulmonary deposits of beeswax that contained either benzo(alpha)pyrene or the heptane-soluble fraction of cigarette smoke condensate. The preneoplastic epithelium was searched for morphological harbingers of neoplasia and compared with the type of reactive bronchial metaplasia, rarely associated with cancer, that results from chronic murine pneumonitis. The carcinogen-laden beeswax caused both proliferation and migration of epithelial cells from bronchi adjacent to the wax deposits. These initial proliferating cells were characterized by a lack of differentiation and were similar to the basal cells of bronchial epithelium. The migrating epithelium rapidly established itself at the interface of wax and viable lung tissue as a highly differentiated, stratified squamous epithelium. This epithelium was not qualitatively different from normal squamous epithelium. However, quantitative differences were evident from both normal epithelium and the metaplastic epithelium resulting from nonspecific injury. In the preneoplastic epithelium, the first indications of aggressive behavior occurred in foci of dysplastic basal cells that sent cytoplasmic intrusions through defects in the basement membrane. Characteristically, these dyplastic basal cells had numerous infoldings of the nuclear membrane and prominent nucleolar alterations. All strata of preneoplastic cells contained excessively complex interdigitations of the plasma membrane and unusually large numbers of desmosomes and tonofilaments. In contrast, the nonspecific metaplastic epithelium consisted almost entirely of multilayered uniform cells that closely resembled immature but otherwise normal basal cells of respiratory epithelium.