Regulation of polyamine biosynthesis by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
We have examined the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on tissue polyamine concentrations in CD1 mice. Two days after a low dose treatment with TCDD, polyamine content of the liver and thymus of treated mice showed a 49-82% decrease, but that of spleen was not affected. Based on this finding, we examined the role of alterations in polyamine levels in the toxicity of TCDD. We administered the polyamine biosynthetic inhibitor difluoromethylornithine (DFMO) to animals treated with a toxic dose of TCDD. DFMO dramatically increased the toxicity of TCDD as measured by mortality, ascites and changes in organ weights. In addition, administration of the polyamine putrescine was able to reduce the toxicity of TCDD. These results suggest that a decrease in polyamine concentrations in critical organs may play an important role in the toxic effects of TCDD.
Thomas
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Department of Environmental and Community Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway 08854.
MacKenzie
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Gallo
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D000818:Animals; D001201:Ascites / Q000139:chemically induced; D001835:Body Weight / Q000187:drug effects; D000518:Eflornithine / Q000633:toxicity; D005260:Female; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D011073:Polyamines / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011700:Putrescine / Q000096:biosynthesis; D013095:Spermidine / Q000096:biosynthesis; D013096:Spermine / Q000096:biosynthesis; D013154:Spleen / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism
D011073:Polyamines; D000072317:Polychlorinated Dibenzodioxins; D013096:Spermine; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine