Joint actions of developmental toxicants in Xenopus embryos: binary mixtures of DNA synthesis inhibitors.
The joint toxic action for each of three binary combinations of DNA synthesis inhibitors was examined at concentrations that induce malformations in Xenopus laevis embryos. The three compounds, hydroxyurea, cytosine arabinoside, and 5-fluorouracil, which each inhibit a different enzyme involved in DNA synthesis, were selected for joint action testing to help determine whether joint action types are related to general modes of action (e.g., inhibit DNA synthesis) or to specific biochemical/molecular mechanisms. Three mixtures were tested, in 96-hr static-renewal tests, for each combination. Each combination was tested on three separate occasions. Using toxic unit analysis, the joint action for induction of malformations was generally antagonism, although response addition was observed for certain mixtures. An antagonistic joint action represents the phenomenon of interaction. Therefore, the tests were ineffective in determining whether a concentration addition joint action depicts two compounds that induce malformations by the same general mode of action or by the same specific mechanism of action.
Dawson
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Department of Animal Science, College of Veterinary Medicine, University of Tennessee, Knoxville 37901-1071.
Wilke
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D000818:Animals; D003561:Cytarabine / Q000633:toxicity*; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects*; D004357:Drug Synergism; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D005472:Fluorouracil / Q000633:toxicity*; D006918:Hydroxyurea / Q000633:toxicity*; D013723:Teratogens / Q000633:toxicity*; D014982:Xenopus laevis
D013723:Teratogens; D003561:Cytarabine; D004247:DNA; D005472:Fluorouracil; D006918:Hydroxyurea