2,3,7,8-Tetrachlorodibenzo-p-dioxin causes elevation of the levels of the protein tyrosine kinase pp60c-src.
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 microgram/kg for guinea pigs, 25 micrograms/kg for rats, and 30 micrograms/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.
Bombick
D W
DW
Pesticide Research Center, Michigan State University, East Lansing 48824-1311.
Matsumura
F
F
D000447:Aldehydes / Q000633:toxicity*; D000818:Animals; D000911:Antibodies, Monoclonal; D001345:Autoradiography; D002478:Cells, Cultured; D004147:Dioxins / Q000633:toxicity*; D006168:Guinea Pigs; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D015688:Oncogene Protein pp60(v-src); D010766:Phosphorylation; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011505:Protein-Tyrosine Kinases / Q000032:analysis*; D051381:Rats; D012191:Retroviridae Proteins / Q000032:analysis*; D013045:Species Specificity; D013950:Thymus Gland / Q000187:drug effects
D000447:Aldehydes; D000911:Antibodies, Monoclonal; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D012191:Retroviridae Proteins; C045934:4-hydroxy-2-hexenal; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src)