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Biomedical subjects

E Borenfreund

Publications and source records attributed to E Borenfreund.

63 records · Page 4Linked to original sources
PubMed1970

Studies of DNA-induced heritable alteration of mammalian cells.

An intercellular interaction between mouse Ehrlich ascites tumor and non-malignant Chinese hamster cells occurred when these were co-cultured. That the intercellular processes which formed had emanated from the EA cells was revealed by immunofluoroscopy using anti-EA antiserum, and by direct microscopic examination. A passage of DNA from the EA to the CH cells was also observed. On long-term co-culture, new cell forms arose which were isolated, cloned, and propagated. They showed a CH karyotype and had acquired oncogenic potential and the ability to synthesize murine-specific antigens. These same heritable properties were also acquired by CH cells following their exposure to DNA isolated from EA cells.

Animals↗
PubMedDate not supplied

Mallory body-like abnormalities in carcinomas induced by cultured transformed rat liver cells.

Hepatoma cells isolated from rats after administration of a carcinogen, diethylnitrosamine, and propagated in culture, contained a genetically stable cytoskeletal abnormality resembling Mallory bodies. These juxtanuclear aggregates of intermediate-sized filaments were maintained in carcinomas produced in nude mice after inoculation of uncloned mass cultures and a cloned subculture. Paraffin and frozen sections of these tumors revealed acentric nuclei and a glassy hyalin-type cytoplasmic lesion which stained pink with hematoxylin-eosin and blue with Mallory's aniline blue stain. The cells in culture and in the tumor sections were strongly positive for gamma-glutamyl transpeptidase. Cryostat sections examined by indirect immunofluorescence microscopy with antisera to purified bovine hoof prekeratin, desmosome-associated tonofilaments from bovine muzzle, and murine vimentin, as well as transmission electron microscopy revealed the presence of juxtanuclear aggregates of intermediate-sized filaments. All characteristics previously reported for the tissue culture cell line were stably maintained in the tumor tissue. These results suggest that the Mallory body-containing cells frequently observed in man in alcoholic hepatitis and other degenerative liver diseases could, under appropriate environmental "promoting" conditions, be precursor cells in focal hepatocellular carcinoma formation.

Animals↗
PubMedDate not supplied

Progress and problems in evaluating and validating alternative assays in toxicology.

Various techniques have been proposed and subsequently developed as potential replacements for whole-animal topical toxicology assays. Comparisons of in vitro and in vivo endpoints, the solubility of test agents, solvent effects, interactions between components of complex test samples and the standardization of data presentation are factors that influence not only individual laboratory results but interlaboratory reproducibility and the acceptance of newly developed alternative methods. Representative alternative test systems for evaluating topical toxicity are discussed. Examples of problems, data and solutions based on the authors' experience and on experience in other laboratories are reviewed. Specific problems in choosing endpoints, comparing results, recognizing responses of different types of target cell, evaluating the influences of support media in culture and interpreting published animal-based data are included.

Animals↗
PubMedDate not supplied

Toxicity determined in vitro by morphological alterations and neutral red absorption.

A method is described which combines the use of a visual morphological cytotoxicity assay with a quantitative neutral red (NR) spectrophotometric test, for the assessment of the effect of toxic agents on 3T3 cells in culture. These sensitive and reproducible assays lend themselves to a screening procedure of potential toxicants which can help reduce the use of animals for toxicity testing.

Animals↗
PubMedDate not supplied

Toxicity monitored with a correlated set of cell-culture assays.

A set of assays for toxicity has been developed in which cell cultures serve as an alternative to toxicity testing in vivo. One test is the assessment of the highest concentration of toxicant which produces minimal morphological alterations in cell cultures, followed by the determination of the amount of neutral red dye uptake by the cells. A second test is based on 50% inhibition of uptake of [3H]uridine after incubation of the cultures with the toxicant. There is good agreement between these assays in the rank correlation of a broad spectrum of compounds tested, as well as with the data from Draize rabbit eye irritancy tests in vivo.

Animal Testing Alternatives↗
PubMedDate not supplied

Mediating role of metabolic activation in in vitro cytotoxicity assays.

Enzymatic activation of polycyclic aromatic hydrocarbons (PAHs) and its effect on cytotoxicity were studied using the neutral red viability assay as the end point. Benzo[a]pyrene was progressively cytotoxic to human hepatoma (HepG2) cells over a 1- to 3-d period, and after induction of monooxygenase activity with a polychlorobiphenyl (PCB) mixture (Arochlor 1254), cytotoxicity was increased about threefold. Concomitant with Arochlor exposure was an increase in the activity of 7-ethoxycoumarin odeethylase, which could be inhibited by exposure to alpha-naphthoflavone. Human keratinocytes (NHEK), but not fibroblasts (HFF), were sensitive to the cytotoxicity of benzo[a]pyrene. However, preexposure of the keratinocytes to Arochlor did not increase their sensitivity to benzo[a]pyrene. Neither the keratinocytes, fibroblasts, nor HepG2 cells were sensitive to acenaphthene. Addition of hamster or rat hepatic S9 mix, however, resulted in toxicity from benzo[a]pyrene and acenaphthene. 7,12-Dimethylbenz[a]anthracene was only mildly cytotoxic to the fibroblasts, and its cytotoxicity was not enhanced in the presence of rat or hamster S9 mix. Exposure of the HepG2 cells to 7,12-dimethylbenz[a]anthracene showed progressive toxicity over a 1- to 3-d period. Prior exposure of the HepG2 cells to Arochlor did not enhance their sensitivity to 7,12-dimethylbenz[a]anthracene. Human keratinocytes were sensitive to 7,12-dimethylbenz[a]anthracene, with cytotoxicity markedly increasing over a 1- to 3-d period.

9,10-Dimethyl-1,2-benzanthracene↗