摘要:

A blocontainment facility was built for studies in which the chemical carcinogenN‐methyl‐N‐nitrosourea (MNU) was instilled intrarectally in guinea pigs. The system operated by constant flow of uncontaminated air into carcinogen‐contaminated animal isolation chambers and filtration through a high‐efficiency particuiate air (HEPA) filter prior to release into the environment. The facility was tested for efficiency of carcinogen containment by substituting for the MNU a similar concentration of a fluorescent tracer, sodium fiuorescein, under standard operating procedures for carcinogen administration to guinea pigs. Wipe samples from the floor, isolation chambers, animal handlers and clothing, and intake and exhaust air samples were analyzed for fiuorescein before and after intrarectal instillation of the tracer. The recovery of very low concentrations of total and respirable suspended fiuorescein from sampling points within the facility and the absence of detectable fiuorescein in the air downstream from the HEPA filter indicated that the facility provided adequate protection against contamination of personnel or the environment.

ISSN:0098-4108    

DOI:10.1080/15287398109529953

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

The effects of chronic treatments with HgCl2on cell survival, DNA replication, and cell progression in cultured Chinese hamster ovary cells were investigated. The ability of these cells to recover from the effects was also characterized. Exposure of cells to 4 × 10−5M HgCl2for 30 min killed about 50% of the cells, and this proportion did not increase with continued exposure up to 24 h. The rate of DNA replication was reduced to 28% of the control rate in the presence of HgCl2. However, when the cells were returned to medium without HgCl2, the rate of DNA replication recovered to 88% of control after 3 h of exposure and 55% of control after 8 h of exposure. The cell doubling time was increased from a control value of 16 h to 31 h in the presence of HgCl2. When the exposed cells were returned to medium without HgCl2, the doubling time returned to 16 h. The rate of progression of cells from G1phase to S phase was greatly reduced in the presence of HgCl2, and no recovery was observed in this case when the cells were transferred to normal medium. These findings suggested a correlation between ability to recover and the cytotoxic effects of HgCl2.

ISSN:0098-4108    

DOI:10.1080/15287398109529954

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

This report describes the results of a long‐term monitoring study of 36 grape harvesters who were occupationally exposed to organophosphate pesticide residues following reentry into vineyards during September and October 1976. The study was designed to evaluate biochemical parameters associated with organophosphate pesticide exposure, to relate the occurrence of changes in these parameters to environmental residues of cholinesterase‐inhibiting pesticides, and to evaluate techniques for monitoring the health of agricultural workers routinely exposed to organophosphate pesticide residues.

ISSN:0098-4108    

DOI:10.1080/15287398109529955

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

Effluents from the bleaching of kraft pulp were tested for mutagenicity. Samples from different mills in which softwood kraft pulp is bleached in a conventional sequence of stages were spot‐tested with theEscherichia colipol A−/pol A* system. All samples were nontoxic and therefore no difference could be noted between the repair‐proficient and the repair‐deficient strain. Also no toxic or mutagenic effects were seen in spot tests with Salmonella.

ISSN:0098-4108    

DOI:10.1080/15287398109529956

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

Daily iv doses of 3 g/kg dimethyl sulfoxide in a 40% solution were given to rhesus monkeys for 9 consecutive days. The monkeys were monitored before and after treatment for 4 mo for changes in blood chemistry, hematology, urine, and ocular, neurological, and cardiovascular systems. At the end of the study all animals were sacrificed and gross and microscopic pathological examinations were performed. No significant or long‐lasting changes were recorded in any of the parameters studied when these data were compared to those for saline controls.

ISSN:0098-4108    

DOI:10.1080/15287398109529957

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

Primary cultures of rat heart cells were used as a model system to study the influence of two antioxidants, vitamin E and ascorbyl palmitate, on biological effects of thermally oxidized fat. The free fatty acid fraction of the distillable non‐urea‐adductable fraction of heated corn oil (HCO) was used as the test lipid; the free fatty acid fraction of fresh corn oil was the control, HCO (100 μg/ml medium) depressed the mitotic index, induced excessive lipid accumulation, and increased the number of pyknotic nuclei in the cells. Addition of extra vitamin E (10 μg/ml medium) reduced the toxicity of HCO by counteracting these changes. In comparison, ascorbyl palmitate (10 μg/ml medium) in the presence of HCO was beneficial in that it produced only a slight increase in the mitotic index. HCO treatment also resulted in reduced levels of linoleic and arachidonic acids in the phospholipid fractions of the cells, and addition of vitamin E or ascorbyl palmitate increased the level of arachidonic acid. The triacylglycerol fraction of HCO‐treated cells showed markedly reduced linoleic acid and increased arachidonic acid. These changes were unaffected by the antioxidant treatments. Vitamin E counteracted the adverse effects of HCO treatment on the rat heart cells. Ascorbyl palmitate only was as efficient as vitamin E in elevating the concentration of arachidonic acid at the membrane level in the presence of HCO.

ISSN:0098-4108    

DOI:10.1080/15287398109529958

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

Guided by structure‐activity relationships among carcinogenic aromatic amines, a sulfur‐containing aromatic diamine was designed as a possible noncarcinogenic replacement for the resin hardener 4,4´‐methylenebis(2‐chloroaniline) (MOCA). However, in small‐scale tests in rats the analog diaminodiphenyldisulfide (DDDS) caused necrotic changes in the liver, acanthosis and hyperkeratosis of the forestomach, and atrophy and hyperplasia of the ductal epithelium of the kidney. One case of hepatocellular carcinoma was also noted. Furthermore, DDDS caused alterations in the phospholipid pattern of liver, kidney, and spleen, increasing total phospholipid and cholesterol but decreasing triglyceride levels. However, it was not mutagenic in aSalmonellatest system, even in the presence of S9 and microsomal fractions from Aroclor 1254‐treated rats.

ISSN:0098-4108    

DOI:10.1080/15287398109529959

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

Primary cultures of hepatocytes from postnatal Sprague‐Dawley rats were grown in arginine‐deficient, ornithine‐supplemented medium to inhibit fibroblastic overgrowth and to selectively isolate relatively pure cultures of parenchymal hepatocytes. This system of primary cultures of rat hepatocytes was utilized to evaluate the cytotoxicity of certain tricyclic antidepressant drugs (TCAs). The compounds tested were chosen to represent two distinct chemical classifications of TCAs: the dibenzazepine derivatives, imipramine (I) and desipramine (D), and the dibenzocycloheptadiene derivatives, amitriptyline (A) and nortriptyline (N). The study also allowed direct comparison of the parent tertiary amines, A and I, and their respective demethylated pharmacologically active metabolites, N and D. The hepatotoxicity of the compounds was determined by measuring leakage of cytoplasmic enzymes, lactate dehydrogenase (LDH) and glutamic‐pyruvic transaminase (GPT), into the culture medium and by assessing cell viability by the trypan blue dye exclusion test LDH leakage was a more sensitive index of early cellular injury in this study. The compounds demonstrated a dose‐ and time‐dependent order of toxicity; their hepatotoxic potency was ranked as A=N > D > I.

ISSN:0098-4108    

DOI:10.1080/15287398109529960

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

Primary cultures of adult rat parenchymal hepaiocytes were developed as an in vitro model to investigate the biochemical fate of 2‐acetylaminofluorene (AAF), a potent hepatocarcinogen. More than 5 × 108viable cells were routinely isolated by collagenase perfusion of rat liver; the cells were cultured 2–5 d on collagen‐coated dishes in serum‐free culture medium containing hormones and other factors to retard the decline of cytochrome P‐450. All of 137 ng or 13. 7 μg AAF was metabolized in 21–24 h by 2 × 106cultured hepatocytes in 4.0 ml defined medium. At the higher dose, water‐soluble metabolites appeared at 70% of the rate of metabolism at the lower dose, which was 17 ng/h for the initial 4 h. As the parent compound was consumed, bound AAF residues were recovered with exhaustively extracted, trichloro‐acetic acid‐precipitated hepatocellular macromolecules, accounting for a maximum of 5% of the 137‐ng dose. Addition of hormones to the culture medium stimulated the rate of appearance of water‐soluble metabolites of AAF, correlating with the enhanced cytochrome P‐450 levels of hormone‐treated cells. Metabolism of AAF was diminished 50% during 3 h of incubation with 10−4M SKF 525A and 100% with 10−3M SKF 525A. At a dose of 40 μg AAF per 2 × 106cells, only 31% of the carcinogen was recovered from the culture medium as water‐soluble products after 24 h; the cells were shown to be capable of metabolizing a subsequent 40‐μg dose at an un‐diminished rate, suggesting that saturation of metabolizing enzymes rather than toxicity occurred. These results support the validity of primary hepatocyte cultures as a model system for quantitative investigations of the biochemical fate of AAF in mammalian cells, and provide preliminary characterization of the cells’ processes of detoxification and metabolic activation of a chemical carcinogen.

ISSN:0098-4108    

DOI:10.1080/15287398109529961

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor

摘要:

Human fecal extracts contain substances mutagenic toSalmonella typhimuriumTA 100. The mutagenicity of these extracts con be reduced enzymatically by inducible mammalian microsomal enzymes. Liver homogenates from rats administered the polychlorinated biphenyl mixture Aroclor 1254 and corn oil were both effective, relative to the quantity of microsomal protein available in the enzyme preparation.

ISSN:0098-4108    

DOI:10.1080/15287398109529962

出版商:Taylor & Francis Group    

年代:1981

数据来源: Taylor