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Biomedical subjects

R E Albert

Publications and source records attributed to R E Albert.

At least 55 records · Page 3Linked to original sources

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↗

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↗

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↗

Dose-dependent effects of submicrometer sulfuric acid aerosol on particle clearance from ciliated human lung airways.

We previously showed that 1 hr exposures to submicrometer sulfuric acid (H2SO4) aerosol at 100 and 1000 micrograms/m3 altered the bronchial mucociliary clearance of monodisperse 7.6 micron MMAD 99mTc-labelled ferric oxide (Fe2O3) in healthy, nonsmoking humans. The 7.6 micron particles were primarily deposited in the larger bronchial airways, where submicrometer H2SO4 has very little deposition. To determine the extent that submicrometer H2SO4 aerosol affects clearance from the more distal ciliated airways, we measured the clearance of a monodisperse 4.2 micron MMAD Fe2O3 aerosol in eight other healthy nonsmoking subjects. A greater fraction of 4.2 micron particles deposited in distal conductive airways. Bronchial mucociliary clearance was slower following 1 h nasal H2SO4 inhalations at 100, 300 and 1000 micrograms/m3 than after sham exposures, while mucociliary transport rates within the trachea and indices of respiratory mechanics were unchanged. A comparison of the effects of 1 h exposures at 100 micrograms/m3 on the clearance of 7.6 and 4.2 micron particles suggests greater physiological response in distal ciliated airways than in larger central airways.

Adult↗

Skin cancer incidence among children irradiated for ringworm of the scalp.

A series of about 2200 children who received X-ray treatment for ringworm of the scalp (tinea capitis) during the 1940s and 1950s, and a comparable group of 1400 treated without X ray, have been followed by mail questionnaire for an average of 26 years since treatment to tabulate the incidence of skin cancer. The X-ray treatment consisted of 300-380 R to five overlapping fields on the scalp, to cause complete depilation. This delivered doses of 300-600 rad to various portions of the scalp, with lower doses to the skin of the face and neck. In the irradiated group, 41 persons have had one or more basal cell carcinomas of the scalp or face while only three have been diagnosed in controls. There was a high prevalence of multiple skin cancers in the irradiated group (80 lesions among 41 cases). The minimum latent period for radiation-induced skin cancers was long--about 20 years--and this may be attributable to the young age of the population. The skin cancer risk was particularly pronounced on the face, where there would be more UVR exposure in addition to X-ray exposure. Lightness of complexion proved to be an important factor in the skin cancer risk. In addition, skin cancers were found only among caucasians, even though 25% of the study population were blacks. These findings suggest that UVR exposure levels or sensitivity to such exposure interact with ionizing radiation exposure in defining skin cancer risk.

Adolescent↗

Comparative carcinogenic potencies of particulates from diesel engine exhausts, coke oven emissions, roofing tar aerosols and cigarette smoke.

Mammalian cell mutagenesis, transformation and skin tumorigenesis assays show similar results in comparing the potencies of diesel, coke oven, roofing tar and cigarette smoke particulates. These assay results are reasonably consistent with the comparative carcinogenic potencies of coke oven and roofing tar emissions as determined by epidemiological studies. The bacterial mutagenesis assay tends to show disproportionately high potencies, particularly with diesel particulates. Results to date encourage the approach to the assessment for carcinogenic risks from diesel emissions based on the use of epidemiological data on cancer induced by coke oven emissions, roofing tar particulates and cigarette smoke with the comparative potencies of these materials determined by in vivo and in vitro bioassays.

Animals↗

Transplacental skin tumor initiation of Ha/ICR mice at different fetal ages.

The initiation of cells in fetal skin was studied by exposing pregnant Ha/ICR mice intragastrically to single doses of a carcinogen at different times during gestation. For comparison, adult mice were exposed to the same carcinogen in a similar manner. The carcinogen, 7,12-dimethylbenz(a)anthracene (DMBA), was given at a dose of about 120 mg/kg in 0.2 ml sesame oil by gavage to 7-week-old pregnant females. The presence of initiated cells in the adult offspring was determined by topical application of 5.0 micrograms in 0.2 ml acetone of the skin tumor promoter tetradecanoyl-12-phorbol-13-acetate to the skin three times weekly beginning at 9 weeks of age. The yield of tumors was determined as a function of time during continuous promotion. Evidence of initiated cells was found in adults exposed transplacentally to DMBA as early as Day 9 of fetal development. The histological characteristics of the tumors and their temporal pattern of development were essentially the same for mice exposed at different stages of fetal development as they were for mice exposed to DMBA as adults. Male and female offspring exhibited approximately the same tumor yields. The use of [3H]DMBA and autoradiographs provided evidence that the cellular dose of DMBA was approximately equivalent at each stage of gestation and in adult skin. The results suggest that the number of initiated cells produced by a given dose of DMBA to the epidermis or fetal ectoderm is proportional to the number of cells in the tissue at the time of exposure.

9,10-Dimethyl-1,2-benzanthracene↗

Cigarette smoke and carbon monoxide do not have equivalent effects upon development of arteriosclerotic lesions.

Experiments were performed to test whether exposure to mainstream cigarette smoke, without any diet modification, was sufficient to exacerbate arteriosclerotic lesion development in cockerels. Additionally, the experiments were designed to test whether any such effect could be attributed solely to carbon monoxide (CO) in the smoke. Three groups of cockerels (7/group) were exposed 5 days/week in standard inhalation chambers. Each day, one group (smoke) was exposed to smoke produced from the combustion of two packs of cigarettes. A second group (CO) was exposed to CO at levels equivalent to those produced during the combustion of two packs of cigarettes. A third group was sham-exposed. Following sacrifice, the abdominal aorta of each animal was cut into 5 mm segments and the extent of arteriosclerotic lesion development was measured. In smoke animals, compared to those in either of the other two groups, there were more aortic segments with measurable lesions present and the cross-sectional areas of these segments were greater. On a comparative basis, the smoke lesions were three times larger than in either of the other two groups, despite the fact that blood carboxyhemoglobin levels were the same in CO and smoke animals. The location of the lesions and their histological appearance were very similar to those previously described for spontaneous and carcinogen-associated lesions in the cockerel. These results demonstrate that as little as four months of daily exposure to cigarette smoke, in the absence of a cholesterol supplemented diet, can help accelerate arteriosclerotic lesion development. Further, this accelerated development cannot be attributed solely to CO in the smoke.

Animals↗

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↗

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↗