The early effects of chemical carcinogens on adult rat hepatocytes in primary culture. II. Effects on unscheduled DNA synthesis, cell division and alpha-fetoprotein production.

The effects of exposure of rat hepatocytes in primary maintenance culture to chemical carcinogens has been studied with respect cytotoxicity and alterations in mitotic index, unscheduled DNA synthesis and alpha-fetoprotein (AFP) production. All compounds tested produced cytotoxicity. Increases in mitotic index and unscheduled DNA synthesis and the production of AFP were observed after treatment of the cells with the carcinogens but not after treatment with the non-carcinogenic isomers. These increases were dose-dependent and depended on the time of exposure and the time incubated postexposure. The patterns of the increase in mitotic index and AFP production after cessation of carcinogen exposure were very similar, with the increase in mitotic index occurring slightly before that for the AFP production and it is suggested from this and other data that the production of AFP is dependent on the generation of a cell species functionally distinct from the non-dividing hepatocytes. It is also suggested that measurement of unscheduled DNA synthesis in conjunction with that of AFP production in cultured hepatocytes may be useful as part of a screening programme for chemical carcinogens.

The early effects of chemical carcinogens on adult rat hepatocytes in primary culture: I. Quantitative changes in intracellular enzyme activities following a single dose of carcinogen.

The effects of exposure of adult rat hepatocytes to chemical carcinogens have been studied using a short-term maintenance culture system. Scanning microdensitometry was used to quantitate the observed changes in enzyme activity. The dose-response curves showed a biphasic response for all 4 enzymes studied (glucose-6-phosphate dehydrogenase, succinate dehydrogenase, NADPH oxidase and gamma-glutamyl transpeptidase) there being decreased enzyme activities at the higher dose levels used, possibly indicating cytotoxicity. The enhancement of enzyme activity at low dose levels was due to generalised increases occurring in every cell, rather than to selection of a cell species particularly high in enzyme activity. A culture period of 24 h was necessary for the complete adaptation of the cells to the culture environment as evidenced by the response of intracellular glucose-6-phosphate dehydrogenase activity to carcinogen treatment. These findings are discussed in relation to previously reported in vivo studies.

Castor bean allergy in the upholstery department of a furniture factory.

In this study, undertaken to identify the cause of allergy in several upholstery workers in a furniture factory, the workers were handling several different materials, including glue, silicone spray, upholstery fabrics, and felt. Radio-allergo-sorbent test (RAST) assays showed that sera from sensitised workers contained specific IgE towards the felt; however, further investigations using RAST showed that the allergen was not the felt itself but a contaminant of the felt. The felt was manufactured from sacks, some of which had been used to store castor beans. The sera with raised IgE to the felt also had raised IgE to the castor bean extract. By means of RAST inhibition we confirmed that castor bean allergens in the felt were solely responsible for the raised IgE in the sera. The in-vitro RAST results were found to correlate well with the in-vivo pick tests and clinical symptoms.

Automated discrete kinetic method for erythrocyte acetylcholinesterase and plasma cholinesterase.

We describe an automated kinetic method for erythrocyte acetylcholinesterase (EC 3.1.1.7) and plasma cholinesterase (EC 3.1.1.8) based on Ellman's colorimetric method. Quinidine sulfate is used as an inhibitor of plasma cholinesterase during the measurement of erythrocyte acetylcholinesterase activity, obviating the need for washing the erythrocytes before lysis. Results by this method are compared with those obtained by the electrometric delta pH method of Michel. To emphasize the need for measuring both erythrocyte acetylcholinesterase and plasma cholinesterase activity in workers exposed to organophosphate pesticides, we present a study of serial activities of both enzymes in a person accidentally exposed to demeton-S-methyl.