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B F Trump

Publications and source records attributed to B F Trump.

At least 19 recordsLinked to original sources
PubMed1992

Studies of skin toxicity in vitro: dose-response studies on JB6 cells.

There are many reasons for developing in vitro tests of toxicity including cost, speed, studies of mechanisms, and studies utilizing human cells and tissues. The present study focuses on the development of in vitro tests to predict in vivo toxicity by comparing them to data from the literature. A broad spectrum of model toxic compounds was evaluated for toxicity on mouse skin JB6 cells in culture. These included mercuric chloride, sodium lauryl sulfate, formaldehyde, dimethyl sulfoxide, benzoyl peroxide, and ionomycin, all of which have been proven to be positive in the Draize test or in cutaneous toxicity studies. Cell viability was evaluated every 15 min for up to 1 hr, and then after 24 hr of treatment using the Trypan Blue exclusion method; morphological changes were evaluated using phase-contrast and transmission electron microscopy. Dose- and time-dependent cell death and morphological changes were observed at concentrations ranging from 10(-14) to 10(-2) M. Arbitrary rankings were assigned based on 1) IC50 value estimated from the present data, and 2) in vivo toxicity reported in the Registry of Toxic Effects of Chemical Substances. Good correlation between in vitro and in vivo toxicity based on arbitrary rankings was observed. Thus, these findings suggest that the JB6 cell culture model can be used for predicting in vivo toxicity. In the future, it may be possible to utilize this system for the study of intracellular ionized calcium ([Ca2+]i), and the expression of oncogenes as early indicators of toxicity.

Animals↗
PubMed1992

Polycyclic aromatic hydrocarbon-DNA adducts and the CYP1A1 restriction fragment length polymorphism.

Human cancer risk assessment at a genetic level involves the investigation of carcinogen metabolism and DNA adduct formation. Wide interindividual differences in metabolism result in different DNA adduct levels. For this and other reasons, many laboratories have considered DNA adducts to be a measure of the biologically effective dose of a carcinogen. Techniques for studying DNA adducts using chemically specific assays are becoming available. A modification of the 32P-postlabeling assay for polycyclic aromatic hydrocarbon DNA adducts described here provides potential improvements in quantification. DNA adducts, however, reflect only recent exposure to carcinogens; in contrast, genetic testing for metabolic capacity indicates the extent to which carcinogens can be activated and exert genotoxic effects. Such studies may reflect both separate and integrated risk factors together with DNA adduct levels. A recently described restriction fragment length polymorphism for the CYP1A1, which codes for the cytochrome P450 enzyme primarily responsible for the metabolic activation of carcinogenic polycyclic aromatic hydrocarbons, has been found to be associated with lung cancer risk in a Japanese population. In a subset of individuals enrolled in a U.S. lung cancer case-control study, no association with lung cancer was found.

Blotting, Southern↗
PubMed1979

Studies on cell surface conformation following injury. II. Scanning and transmission electron microscopy of cell surface changes following anoxic injury in Ehrlich ascites tumor cells.

Exposure of Ehrlich ascites tumor cells to anoxia resulted in rapid and characteristic conformational changes of cell surface topography. Combined scanning and transmission E/M studies revealed rapid alterations including simplification of the cell surface configuration with disappearance of microvilli which were replaced with formation of blebs and recesses at the cell periphery. These surface changes were accompanied by characteristic organelle alterations inside the cells which in this and other cellular systems have been shown to be reversible. Later, the cell surface topography became smoother and monotonic with small blebs and cribriform invaginations in addition to larger eruptions of the cell periphery. Combined transmission E/M studies revealed fragmentation of cellular membrane systems and lysis of organelles indicating the irreversible phase of anoxic injury. The rapid conformational surface changes encountered in Ehrlich ascites tumor cells following anoxia suggest the important role of the plasma membrane and its unfolding as a virtually instantaneous response of the cells to this injury.

Animals↗
PubMed1979

Long-term culture of human aortas. Development of atherosclerotic-like plaques in serum-supplemented medium.

Segments of human thoracic aorta were maintained in long-term explant culture for 18 weeks in serum-supplemented medium. The aortas were grossly normal in appearance, and random samples fixed for light microscopy prior to culture revealed a normal morphology. The intima contained no more than five layers of smooth muscle cells. After 7 days in culture, the intima was noticeably thicker than the uncultured segments. The increased thickness was due to proliferating smooth muscle cells and production of extracellular material. After several months in culture, extracellular material consisting of collagen and flocculent material was present in areas resembling atherosclerotic fibrous plaques. A peripheral growth, which formed around the explant, was composed of fibroblastlike cells and added to the overall thickness of the intima. However, aortic segment maintained for up to 2 months in serum-free culture medium showed no cellular proliferation. This study demonstrates that changes resembling early stages of atherosclerosis occur in human aortas maintained in explant culture using routine culture procedures.

Adolescent↗
PubMed1979

Iron negative foci and nodules in safrole-exposed mouse liver made siderotic by iron-dextran injection.

A procedure for the production of mouse hepatic siderosis is described which results in extensive iron deposition in all lobular zones. Mice exposed to safrole for 24 weeks displayed basophilic and acidophilic foci which did not accumulate iron. 36 weeks of dietary safrole exposure resulted in nodular lesions comprised of basophilic and hyalinized cells. The nodules displayed decreased or negative reactions for iron in hepatic parenchymal cells when the surrounding liver was siderotic.

Animals↗
PubMed1979

Induction of ouabain-resistant mutation and sister chromatid exchanges in Chinese hamster cells with chemical carcinogens mediated by human pulmonary macrophages.

Pulmonary macrophages (PAM) metabolically activated benzo[a]pyrene [B(a)P] and its proximate carcinogenic metabolite, (+/-)trans 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (7,8-diol), to ultimate mutagens that were detected in cocultivated Chinese hamster V79 cells. Increases in the frequency of ouabainresistant (O(r)) mutations and sister chromatid exchanges were found in V79 cells only when they were cocultivated with both PAM and the chemical procarcinogens. 7,8-Diol caused higher frequencies of both O(r) mutations and sister chromatid exchanges than did the parent compound, B(a)P. When metabolically activated by PAM the mean O(r) mutation frequency caused by B(a)P was 9 O(r) mutants/10(6) surviving V79 cells per 10(6) PAM and a 10-fold interindividual variation (range, 2-21) was found. The mean O(r) mutation frequency caused by 7,8-diol was 64 and a ninefold interindividual variation (range, 14-120) was found. In the absence of PAM, the O(r) mutation frequency in V79 cells was one or less O(r) mutant per 10(6) survivors. 7,8-Benzoflavone, an inhibitor of mixed function oxidases, reduced the frequencies of O(r) mutations and of sister chromatid exchanges in V79 cells caused by 7,8-diol and B(a)P. As expected 7,8-benzoflavone did not influence the frequency of O(r) mutations caused by one of the ultimate mutagens derived from B(a)P and 7,8-diol, (+/-)7beta, 8alpha-dihydroxy-9alpha, 10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene. These data are consistant with the hypothesis that PAM may play a role in the activation of environmental chemical procarcinogens.

Adenocarcinoma↗
PubMed1979

The respiratory epithelium. VII. Epidermoid metaplasia of hamster tracheal epithelium during regeneration following mechanical injury.

Regeneration was studied in female Syrian golden hamster tracheal epithelium. The epithelium was focally removed in vivo by scraping it with a blunt probe. At 2 hours, virtually all cells had sloughed from the injured area leaving a bare basal lamina. At 6 and 12 hours, flattened cells that migrated from adjacent uninjured epithelium partially covered the denuded basal lamina. Increased cell division did not occur at these times. Many of the simple squamous cells contained well-developed endoplasmic reticulum, Golgi apparatus, and mucous granules. Other cells resembled basal cells. At 24 hours the defect was covered by one or two layers of simple squamous cells. At that time, many of those cells were in division, and cell division was also greatly increased in mucous cells and basal cells in the uninjured epithelium distant from the defect. At 48 hours the epithelium was stratified, composed of four or five layers of polygonal to flattened cells, typical of nonkeratinizing epidermoid metaplasia. The cells contained many tonofilament bundles, a large Golgi apparatus, and many tiny mucous granules. Mitoses were seen in all cell layers. At 72 hours, the surface layer of cells was undifferentiated (indifferent cells) overlying an epithelium that otherwise retained its epidermoid character. Indifferent cells were characterized by an electron-lucent cytoplasm and a lack of tonofilament bundles, mucous granules, or cilla. Cells similar in other respects to indifferent cells were seen that possessed mucous granules or early signs of cilla formation. Some cells showed mucous granules and cilla developing in the same cell. By 96 hours, the regenerated epithelium was fully differentiated and was indistinguishable from the normal epithelium. These observations show that mucous cells have a significant role in the regenerative response. Mucous cells have a dual potential; they can undergo epidermoid metaplasia and still retain the ability to secrete mucus. The study explains the universal occurrence of mucosubstances in areas of epidermoid metaplasia and makes more understandable the previously reported fact that many bronchogenic carcinomas are combined epidermoid and adenocarcinomas. In the presence of a carcinogen, the hypothesis has been forwarded that initiation of mucous cells and basal cells occurs, which leads to malignant transformation and produces tumors that show active secretory activity and keratinization, often in the same cell.

Animals↗
PubMed1979

Induction and properties of aryl hydrocarbon hydroxylase in bovine pancreatic ducts.

Inducibility and characteristics of aryl hydrocarbon hydroxylase (AHH) in cultured bovine pancreatic ducts were studied by the fluorometric method. AHH was present and inducible in all the pancreatic ducts studied when they were exposed to 20 microgram benz[a]anthracene (BA)/ml medium. AHH activity in the control tissue ranged from 1.0 to 3.0 U/mg DNA, whereas the activity in the BA-treated tissue was 4.2--28.5 U/mg DNA, which resulted in the induction of 5- to 18-fold activity. At 12 hours of BA exposure, AHH activity in the treated tissue was 12-fold that in the control tissue and continued to increase to 15-, 19-, and 31-fold that in the control tissue at 24, 48, and 72 hours, respectively. The BA-induced AHH activity had a broad pH optimum between 7.1 and 7.7, and the maximum activity was found at pH 7.4. The AHH activity was linear with respect to the incubation time up to 30 minutes. The effect of the benzo[a]pyrene concentration on AHH activity was studied on the BA-induced enzyme. The apparent Michaelis constant for the substrate was 0.5 microM, and the maximum velocity was 8.6 U/mg DNA. BA-induced AHH activity was inhibited 65% by 100 microM 7,8-benzoflavone, whereas the control enzyme activity was stimulated 100% by the same concentration of 7,8-benzoflavone.

Animals↗
PubMed1979

Metabolism of aflatoxin B1 and identification of the major aflatoxin B1-DNA adducts formed in cultured human bronchus and colon.

Aflatoxin B1 and benzo(a)pyrene were activated by both cultured human bronchus and human colon as measured by binding to cellular DNA and protein. The binding of aflatoxin B1 to DNA was dose dependent, and the level of binding was higher in cultured human bronchus than it was in the colon. When compared to aflatoxin B1, the binding level of benzo(a)pyrene to both bronchial and colonic DNA was generally higher. The major adducts formed in both tissues by the interaction of aflatoxin B1 and DNA were chromatographically identical to 2,3-dihydro-2-(N7-guanyl)-3-hydroxyaflatoxin B1 (Structure 1) with the guanyl group and hydroxy group in trans-position and an adduct which has been tentatively identified by other investigators as 2,3-dihydro-2-(N5-formyl-2',5',6'-triamino-4'-oxo-N5-pyrimidyl)-3-hydroxyaflatoxin B1 (Structure 11). Seventy % of the radioactivity associated with bronchial DNA was found in these two peaks, and the ratio of radioactivity between the peaks was nearly 1. In colonic DNA, the ratio between Structures 1 and 11 was approximately 2. These observations add aflatoxin B1 to the list of chemical procarcinogens metabolized by cultured human tissues and in which the carcinogen-DNA adducts are similar to the adducts formed in animal tissue susceptible to the carcinogenic action of aflatoxin B1.

Aflatoxins↗
PubMed1979

The subcellular pathology of shock in trauma patients: studies using the immediate autopsy.

In summary, our immediate autopsy program provides a new tool for investigating the pathophysiologic effects of shock and trauma at the cellular and subcellular levels. By minimizing the time delay between death and tissue sampling with this technique, we have demonstrated the feasibility of validly applying the refinements of electron microscopy, histochemistry and analytical biochemistry to human tissue. Qualitative, semi-quantitative and quantitative data with these techniques have been integrated with clinical, physiologic and chemical studies on these patients during life. Cell injury produces an altered steady state of metabolism within the cell, evidence of which is seen in altered ultrastructure. If the injury is too severe, the cell will pass the "point-of-no-return," at which time the changes in the cell are no longer compatible with life and the cell dies and undergoes necrosis. Although the initiating injury and the patterns of the altered steady state may vary, once the cell has passed the "point-of-no-return," the patterns of cell injury regardless of the initial insult, are similar. We believe that the cellular patterns seen in patients dying from shock and trauma are remarkably similar to those produced by hypoxic tissue injury in experimental systems. Tissue from control patients in whom ischemic injury due to episodes of hypotension did not occur show good morphologic preservation with normal mitochondria and other cell organelles. Tissue from patients who have experienced acute shock consisting of a period of hypotensive ischemia show changes in the mitochondria and ER compatible with the experimental picture of hypoxia: i.e., dilated ER, with loss of ribosomes, swelling of mitochondria and the appearance of flocculent densities in the mitochondria. Tissues taken from the patients who had experienced repeated episodes of shock, whom we designated as those in "chronic shock," showed changes paralleling the acute changes, but also showed much evidence of autophagocytosis as a) the cells attempted to achieve a lower metabolic requirement in order to survive, and b) they attempted to "clean-up" and remove altered and damaged organelles and debris from previous bouts with sublethal ischemic injury. We hope that the increased knowledge of tissue and cellular injury obtained by the immediate autopsy will provide a means of integration, hypothesis formation and testing of the vast knowledge of cell biology and pathology, and the opportunity for developing in the human the potential for testing new hypotheses in model systems resulting in immediate and innovative feedback for the patient in terms of diagnosis, functional monitoring and treatment.

Adult↗