PubMed Health⌕ Search

Biomedical subjects

C A Snyder

Publications and source records attributed to C A Snyder.

At least 55 records · Page 3Linked to original sources
PubMed1985

Carcinogenicity of formaldehyde and hydrogen chloride in rats.

Previous studies in this laboratory have shown that the combined exposure of hydrogen chloride (HCI) and formaldehyde vapors (HCHO) elicited a significant incidence of nasal cancer in rats. In studies performed elsewhere, it has been demonstrated that exposure to formaldehyde alone induced a high nasal cancer response in rats. We wished to determine whether concurrent exposure of hydrogen chloride would enhance the tumorigenic effects of formaldehyde. Two exposure techniques were used. In one hydrogen chloride and formaldehyde were premixed at high concentrations before entry into the exposure chambers in order to maximize the formation of reactive alkylating agents. In the second the hydrogen chloride and formaldehyde were introduced separately into the exposure chamber. Appropriate control exposures consisting of formaldehyde alone or hydrogen chloride alone or air alone were also performed. The results show that nasal cancer incidences were induced in all animals receiving HCHO regardless of concurrent exposure to hydrogen chloride. The tumors were predominantly squamous cell type arising from the anterior portion of the nasal cavity. This study demonstrates that hydrogen chloride does not appreciably influence the nasal carcinogenicity of formaldehyde.

Animals↗
PubMed1985

Protracted exposure of C57BL/6 mice to 300 ppm benzene depresses B- and T-lymphocyte numbers and mitogen responses. Evidence for thymic and bone marrow proliferation in response to the exposures.

Groups of C57BL/6J, male mice were exposed to 300 ppm benzene via inhalation for 115 exposures (6 h/day, 5 days/week), a regimen known to cause thymic lymphoma in these animals. The effects of these exposures on lymphoid parameters were determined by measuring the numbers of B- and T-lymphocytes and mitogen-induced proliferation of B- and T-lymphocytes in bone marrow, spleen, and thymus after 6, 30, and 115 exposures. The numbers of B-lymphocytes in bone marrow and spleen and the numbers of T-lymphocytes in thymus and spleen were found to be markedly reduced after all 3 periods. Mitogen-induced proliferation of bone marrow and splenic B-lymphocytes exhibited a progressive depression throughout the exposure period reaching a point of no observable response after 115 exposures. Splenic T-cell mitogen-induced proliferation was also markedly depressed throughout the exposures, but there was no evidence of a progressive decline in this response during the exposures. Bone marrow cellularity increased 3-fold and the numbers of thymic T-cells increased 15-fold in benzene-exposed mice between the 6th and 30th exposure. No corresponding increase in splenic cells was observed in benzene-exposed mice during this interval. The marked increases in the numbers of cells in bone marrow and thymus are interpreted as arising from compensatory proliferation of a subpopulation of cells in response to the exposures. The absence of increases in cell number in the spleen is interpreted as reflecting the lack of lymphoid restorative capacity in this organ. The marked increases of thymic and bone marrow cellularity are discussed relative to the known ability of this benzene exposure regimen to produce thymic lymphoma in these animals.

Animals↗
PubMed1985

Carcinogen specificity in the activation of transforming genes by direct-acting alkylating agents.

DNAs from rat nasal and mouse skin carcinomas and fibrosarcomas induced by the alkylating agents methylmethane sulfonate (MMS), beta-propiolactone (BPL), and dimethylcarbamyl chloride (DMCC) were tested for their ability to transform NIH3T3 cells by DNA transfection. Each of eight MMS-induced rat nasal carcinomas and two of five BPL-induced mouse skin tumors were positive in the transfection assay while all of four fibrosarcomas and six carcinomas induced by DMCC were negative. Anchorage independent growth, tumorigenicity in nude mice, and secondary transfection confirmed the transformed phenotype of the positive transfectants. The transfectants from MMS-induced tumor DNAs did not contain restriction fragments homologous to rat H-, K- or N-ras oncogenes although exogenous (rat) tumor-derived DNA sequences were detected in transfectant genomes by Southern analysis. In contrast a BPL-induced mouse skin tumor showed evidence of containing activated H-ras. These results suggest specificity among causal chemical carcinogens for activation of transforming genes in experimental tumors.

Alkylating Agents↗
PubMed1984

The effects of ethanol and the role of the spleen during benzene-induced hematotoxicity.

Splenectomized and spleen-bearing mice were used to explore the source of nucleated red blood cells (normoblasts) appearing in the peripheral blood of animals treated with both benzene and ethanol and the role of splenic hematopoiesis in compensating for bone marrow stresses by repeated benzene and ethanol exposure. Regardless of operative status, mice exposed to the combined treatment demonstrated a transient appearance of normoblasts in the peripheral blood. Thus, the marrow is the apparent source of the peripheral normoblasts. This condition was not observed in mice treated with only benzene or with only ethanol. Splenectomy significantly influenced bone marrow response to the hematotoxic effects of benzene alone as well as the combined treatment of benzene and ethanol, as evidenced by altered marrow normoblast and granulocyte equilibria.

Animals↗
PubMed1984

Evidence for hematotoxicity and tumorigenesis in rats exposed to 100 ppm benzene.

A group of 40 Sprague-Dawley rats was exposed to 100 ppm benzene for 6 h/day, 5 days/week for life. Another group of 40 rats received air under the same exposure regimen. During the exposures, treated rats exhibited continuously depressed peripheral erythrocyte and lymphocyte counts. Although the incidences of these peripheral cell depressions were statistically significant, the magnitudes of the depressions were not. Histopathologic evaluation revealed that splenic hemosiderin pigments were much more prevalent in exposed rats than in controls, indicating either red cell hemolysis or ineffective erythropoiesis. The mortality-corrected tumor incidences between exposed and control mice were not statistically different. However, several exposed rats died with tumors that, because of their rare spontaneous incidence, are most likely treatment-related. Four rats died with liver tumors, two died with zymbal gland carcinoma, and one died with chronic myelogenous leukemia.

Air Pollutants↗
PubMed1984

The temporal relationship between behavioral and hematological effects of inhaled benzene.

The time-effect relationship of the behavioral and hematological changes caused by inhaled benzene was investigated in C57BL mice. Mice were exposed to air, or 100, 300, 1000, or 3000 ppm benzene in standard inhalation chambers employing dynamic vapor exposure techniques. Mice were exposed for 6 hr/day for the number of days necessary to achieve a minimum concentration X time (Ct) product of 3000 ppm-days. The intermittent exposure regimen of 6 hr/day was employed to simulate occupational exposure. The most sensitive behavioral index (milk-licking) was affected by the lowest concentration tested (100 ppm), while homecage food intake, hindlimb grip strength, and body weight were reduced only at 1000 and 3000 ppm. Some of these previously undocumented behavioral changes occurred as rapidly as hematological changes that have been considered hallmarks of benzene toxicity. A significant decrease in circulating lymphocytes occurred after exposure to all concentrations. Circulating red blood cells were variably affected by benzene, in that anemia resulted after 10 days exposure to 100 ppm and after 3 days exposure to 300 ppm but not after 3 days exposure to 1000 ppm or a single exposure of 3000 ppm. The data indicate a departure from Ct relationships, and suggest that exposure duration as well as daily dose may be an important factor in benzene toxicity.

Aerosols↗
PubMed1984

The effects of ethanol ingestion and repeated benzene exposures on benzene pharmacokinetics.

Two groups of C57Bl/6J mice were exposed to 300-ppm benzene vapor, 6 hr/day, 5 days/week for 20 exposures. One group received 10% ethanol (EtOH) in the drinking water commencing 20 hr prior to the initial exposure and continuing 5 days/week throughout the study. The second group received tap water. The uptake and clearance of benzene was followed in the blood during and after the 1st and 20th exposures. During the first benzene exposures, the mean steady state benzene concentrations in benzene/EtOH-treated mice and benzene/water-treated mice were 5.2 and 10.7 micrograms/ml, respectively. The mean elimination rate constants for the benzene/EtOH- and benzene/water-treated groups were 0.124 and 0.042 min-1, respectively. By 20 exposures, the benzene/EtOH group showed no change in mean blood steady state concentration (Css); however, the Css of the benzene/water group was reduced to 7.9 micrograms/ml. The mean elimination rate constants for the two groups were not different after the 20th exposure. The benzene/water mice exhibited a shift from mono-to biexponential clearance between the 1st and 20th exposures. Monoexponential clearances were observed for the benzene/EtOH group at both time points. These results indicate that 1 day of 10% EtOH consumption causes dramatic effects on benzene kinetics. After 20 days of treatment, the benzene/water and benzene/EtOH animals are kinetically similar. These changes in kinetics can be explained by the ability of ethanol and benzene to alter benzene metabolism.

Animals↗
PubMed1984

Repeated exposure of C57Bl mice to inhaled benzene at 10 ppm markedly depressed erythropoietic colony formation.

Exposure of C57Bl mice to 10 ppm benzene (the current occupational exposure limit) for 6 h/day, 5 days/week causes a progressive depression in the in vitro colony forming ability of one of the erythroid progenitor cells, the colony-forming unit-erythroid (CFU-E). Colony growth of cells from exposed mice was only 5% of control colony growth after 178 days of exposure. Burst-forming-cell growth was depressed to 55% of control growth after 66 days but returned to control growth values at 178 days. In addition, benzene-exposed mice exhibited depressions in the numbers of splenic nucleated red cells and in the numbers of circulating red cells and lymphocytes. These results suggest that low-level exposure to benzene may be hematotoxic.

Animals↗
PubMed1984

Depressions in B- and T-lymphocyte mitogen-induced blastogenesis in mice exposed to low concentrations of benzene.

In a short-term (6 h/day X 6 days) benzene inhalation dose-response study, mitogen-induced blastogenesis of both B- and T-lymphocytes in male, C57Bl mice was observed to be significantly depressed at relatively low levels of benzene. Exposure to 10 ppm benzene resulted in a significant depression in femoral lipopolysaccharide (LPS)-induced B-colony-forming ability, while total numbers of B-lymphocytes at this concentration were not significantly depressed. Similarly, splenic phytohemagglutinin (PHA)-induced blastogenesis was significantly depressed at 31 ppm, without a concomitant significant depression in numbers of T-lymphocytes. These data indicate that concentrations of benzene at or near the current standard for occupational exposure (10 ppm) can affect certain immune-associated processes.

Animals↗
PubMed1983

A single feed system for maintaining different vapor concentrations in two inhalation chambers.

Two different concentrations of the same vapor can be maintained in adjacent dynamic inhalation chambers by using a single feed system which incorporates constant feed air flow rates and efferent tubes of unequal dimensions. For a given set of efferent tubes, the ratio of the air flow rates exiting the feed system and the resultant ratio of chamber concentrations vary as biexponential functions of the net negative pressure applied across the feed system. Depending on efferent tube dimensions and the negative pressure applied across the system, concentration ratios in the two chambers can be varied from 1:1 to 1:10. Three separate 30-day exposures were conducted using the system and observed mean daily vapor concentrations were within 3% of target concentrations.

Air Movements↗
PubMed1982

Myelogenous leukemia in rodents inhaling benzene.

Studies during the past five decades have failed to demonstrate myelogenous leukemia in laboratory animals exposed to benzene despite epidemiologic evidence linking such exposure to myelogenous leukemia in man. We report four cases of myeloproliferative disease among rodents exposed to benzene, 6 h a day, 5 days weekly, for life. There was one case of chronic myelogenous leukemia, one of acute myeloblastic leukemia, and one of granulocytic hyperplasia among 40 CD-1 mice exposed to 300 ppm benzene; and one case of chronic myelogenous leukemia among 40 rats exposed to 100 ppm benzene. Although not statistically significant as compared to the respective control groups, the fact that myelogenous leukemia has not been reported in control animals of these two strains is suggestive of a causative role for benzene.

Animals↗
PubMed1982

Gaseous formaldehyde and hydrogen chloride induction of nasal cancer in the rat.

The carcinogenic response to the combined and separate exposures to formaldehyde (HCHO) and hydrochloric acid (HCl) was investigated in male inbred SD rats. The rats were exposed to gaseous HCHO, 14 ppm, and HCl, 10 ppm, in two experiments. In one experiment the gases were premixed at high concentrations before being diluted in the exposure chamber air to maximize the formation of the carcinogen bis(chloromethyl)ether (BCME). In the second experiment exposure was repeated to HCl and HCHO premixed at high concentrations, and not premixed (to minimize BCME formation), as well as to HCHO alone and HCl alone. The second experiment is being reported on at an interim stage. HCHO alone induced squamous carcinomas of the nasal cavity as did the combined exposures to HCHO and HCl. No carcinogenic response was observed with HCl alone. HCHO accounted for most, if not all, of the carcinogenic activity of the mixture of HCHO-HCl.

Animals↗