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Keywords:

  • TCDD;
  • protein tyrosine kinase;
  • src-protein

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been found to cause increases in cellular levels of pp60src, a protein tyrosine kinase in hepatocytes from the rat and guinea pig, in the thymus of the mouse in vivo and in NIH-3T3 mouse fibroblast cell lines in vitro. Such cellular changes take place in vivo at early stages of TCDD poisoning (as early as one day after treatment in the case of mouse thymus) and at very low doses (single intraperitoneal injections of 1 μg/kg for guinea pigs, 25 μg/ kg for rats, and 30 μg/kg for mice). In addition such an effect of TCDD was observed only in a TCDD-responsive mouse strain but not in a nonresponsive strain. This effect of TCDD is a long-lasting one (eg, even 25 days after single dosing, the levels of pp60src in the hepatic membrane remained high). In vitro this effect was observed in a wild-type 3T3 cell line but was more pronounced in one of the transfected lines with a v-src gene, a virus-derived oncogene known to code for pp60src protein.