The Responce of Adult Rat Sertoli Cells, Immortalized by a Temperature-sensitive mutant of SV40, to 1,2-dinitrobenzene, 1,3-dinitrobenzene, 2,4-dinitrotoluene, 3,4-dinitrotoluene, and cadmium

Cell Biology and Toxicology (Impact Factor: 2.68). 04/2003; 19(2). DOI: 10.1023/A:1023359222963
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In this study we test the hypothesis that immortalized adult rat Sertoli cells respond to known testicular toxins in a similar manner to Sertoli cells tested in vivo and in primary culture. This cell line was developed by immortalizing adult rat Sertoli cells with the temperature-sensitive mutant of SV40, ts255, such that the cells proliferate at the permissive temperature of 33°C but express differentiated characteristics at the nonpermissive temperature of 40°C. Confluent monolayers, grown at 33°C or 40°C, were exposed to a range of concentrations of dinitrobenzene (DNB) or dinitrotoluene (DNT) isomers or to cadmium chloride. Cellular response was assessed by neutralred cell viability assay and ultrastructural changes. Cells grown at 40°C were sensitive to lower concentrations of each toxicant than were cells grown at 33°C. 1,2-DNB was more toxic than 1,3-DNB, and 3,4-DNT was more toxic than 2,4-DNT, as judged by the neutral-red cell viability assay. Ultrastructurally, cells treated with 1,2-DNB or 2,4-DNT showed increased numbers of autophagic vesicles compared to controls. Intercellular penetration of ruthenium red demonstrated breached tight junctions in 1,2-DNB and cadmium-treated cells. From these observations, we conclude that this cell line can serve as a model for studying toxic mechanisms in adult Sertoli cells.

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