Developmental differences in elimination of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during Xenopus laevis development.
Although 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) is a potent developmental toxicant in most vertebrates, several frog species are insensitive to TCDD, especially during early life stages. Previous experiments with ranid frogs suggest that TCDD insensitivity results largely from rapid elimination. Recent studies in the African clawed frog (Xenopus laevis; family Pipidae) link low TCDD toxicity with the low binding affinity of aryl hydrocarbon receptors, which mediate the toxic effects of dioxin-like compounds. The present study sought to examine TCDD elimination in X. laevis embryos and tadpoles, enabling an integrated assessment of the relative roles of TCDD elimination and AHR-related mechanisms in TCDD insensitivity within a single frog species. Using tadpoles (stage 52-55; approximately 1 month old) exposed to [3H]TCDD, we observed that TCDD has a relatively short half life of 102.6 h, consistent with other frogs and much faster than reported clearance rates in developing fish. In contrast, TCDD elimination is much slower during early development. Embryos exposed during primary organogenesis (from stage 31-41, beginning approximately 36 h after fertilization) exhibited little TCDD elimination during the subsequent 96 h. Enhanced TCDD clearance in later developmental stages may follow the appearance of a functional digestive tract and the onset of feeding. These results suggest that rapid elimination is unlikely to contribute mechanistically to TCDD insensitivity during development of the cardiovascular system, which is significantly perturbed by TCDD in fish embryos.
Philips
Blythe H
BH
Biology Department, Kenyon College, Gambier, OH, USA.
Susman
Thomas C
TC
Powell
Wade H
WH
D000818:Animals; D004625:Embryo, Nonmammalian / Q000378:metabolism; D006207:Half-Life; D006321:Heart / Q000187:drug effects / Q000196:embryology; D007814:Larva / Q000378:metabolism; D008657:Metabolic Clearance Rate; D000072317:Polychlorinated Dibenzodioxins / Q000032:analysis / Q000493:pharmacokinetics*; D013997:Time Factors; D014316:Tritium / Q000032:analysis; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000493:pharmacokinetics*; D014982:Xenopus laevis / Q000254:growth & development / Q000378:metabolism*
D000072317:Polychlorinated Dibenzodioxins; D014874:Water Pollutants, Chemical; D014316:Tritium