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Biomedical subjects

E Longstaff

Publications and source records attributed to E Longstaff.

31 records · Page 2Linked to original sources

Evaluation of six short term tests for detecting organic chemical carcinogens and recommendations for their use.

Six short term tests for detecting carcinogenicity have been evaluated using 120 compounds, of which half were carcinogens and the rest non-carcinogens. The results obtained indicate that the Ames test and a "cell transformation" assay are both sufficiently sensitive to carcinogenicity, or the lack of it, in the compounds studied to enable them to be employed for detecting potential carcinogens. The consequences of using short term tests under various screening conditions have been explored. In order to have confidence in the results obtained for new or previously untested compounds it is important to use such tests in a carefully controlled manner.

Alkylating Agents↗

Stimulation of cellular ingestion by basic proteins in vitro.

The ingestion of carbon and benzpyrene particles in vitro by rat peritoneal macrophages, baby hamster kidney fibroblasts (BHK-21) and mouse L-cells has been shown to be significantly stimulated by the inclusion of histone or polylysine in the culture medium. Parallel studies using methylated bovine albumin did not significantly stimulate carbon or benzpyrene uptake relative to untreated control cultures. Incubation of carbon particles with histone before inclusion in the culture medium of macrophages resulted in the same degree of uptake as in the cultures where carbon and histone were added independently of each other. The implications of these findings to in vivo chemical carcinogenesis are examined.

Animals↗

Anti-tumour activity of aprotinin.

A malignant invasive fibrosarcoma in hamsters and a malignant mammary carcinoma in mice were each challenged with the broad spectrum proteinase inhibitor aprotinin (Trasylol). In both tumour systems, significant anti-tumour effects of aprotinin were observed. Variations in the site and dosage of aprotinin application were made in an attempt to improve the chemotherapeutic response.

Adenocarcinoma↗

Enhanced malignant behaviour of cells treated with crude rat liver histone.

Neonatal hamster kidney cells (BHK21/C13), challenged in monolayer culture for three days with crude rat liver histone, have been shown to exhibit increased malignant characteristics when injected subcutaneously into hamsters. In contrast to the controls, the challenged cells produced tumours which invaded either the epidermis or the body wall of their hosts and frequently caused extensive visceral metastases. In vitro studies of the cell cultures, during and after histone treatment, suggested that cellular "transformation" rather than selection was effected by the crude histone preparation. Cells from the primary tumours of both control and test groups appeared morphologically identical but after sub-culture in vitro they retained their respective growth characteristics on reinoculation.

Animals↗

Inhibition of malignant cell invasion in vitro by a proteinase inhibitor.

The inhibitory effect of the protease inhibitor aprotinin (Trasylol) on the invasion of mouse kidney explants by polyoma virus transformed BHK21 cells was investigated using a mixed cell/organ culture technique. The extent of invasion was monitored by following the changes in LDH isoenzyme pattern in the explants and by histological assessment. The kidney explants containing aprotinin were found to maintain a normal kidney LDH pattern and to suffer considerably less invasion than the explants not containing the drug. These results support the idea that proteolytic enzymes are associated with invasion and that inhibitors of protease activity could possibly be useful in the management of clinical cancer.

Animals↗

Transformation of mammalian cells by crude histones.

A baby hamster kidney cell line (BHK21), maintained in the presence of crude histone preparations for 3 days, has been shown to undergo morphological and behavioural transformations similar in nature to those obtained with viruses and mycoplasmas.

Animals↗

Invasive properties of histone transformed cells.

A technique was developed to study the invasion of cells into mouse kidney cortex in the presence of crude rat liver histone at a medium concentration of 100 μg./ml. A marked increase in the invasiveness of normal cells occurred in the presence of histone. Possible explanations of this phenomenon are discussed. The invasiveness was compared with that of cells previously transformed with polyoma virus.

Animals↗