Embryotoxicity of human sera from patients treated with isotretinoin

Van Maele, Geneviève;Therasse, P.;Lenoir, E.;Desager, Jean-Pierre;Picard, Jacques;et.al.
(1993) Toxicology in Vitro — Vol. 7, n° 6, p. 809-815 (1993)

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Authors
  • Van Maele, GenevièveUCLouvain
    Author
  • Therasse, P.UCLouvain
    Author
  • Lenoir, E.UCLouvain
    Author
  • Desager, Jean-PierreUCLouvain
    Author
  • Despontin, KarineUCLouvain
    Author
  • Author
  • Jacobs, Marie-ClaudeUCLouvain
    Author
  • Lecart, C.UCLouvain
    Author
  • Berthet, P.UCLouvain
    Author
  • Lachapelle, Jean-MarieUCLouvain
    Author
  • Picard, JacquesUCLouvain
    Author
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Abstract
Sera of 20 patients treated with 20-40 mg isotretinoin/day were tested for embryotoxicity potential. For each patient, the first sample was taken before treatment (control sample) and the second was taken 2 months after the start of treatment (treated sample). Six embryos displaying six or seven pairs of somites were cultured for 26 hr in each serum sample, when sufficient serum was available. No deaths were observed in the control sample, whereas dead embryos (6%) were observed in the treated sample. The rates of malformed embryos were 13 and 81% in the control and in the treated sample, respectively. The most frequent abnormalities affected the cephalic neural tube, the branchial bars, the yolk sac circulation and the caudal neural tube. Growth and differentiation were significantly decreased in the treated sample. The concentrations of isotretinoin and of two metabolites (trans-retinoic acid and 4-oxo-isotretinoin) were measured in 12 sera. A correlation between embryotoxicity and concentration was established for two of the chemicals. Modulation of the embryotoxicity by drug-induced changes in the serum cannot be excluded.
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Citations

Van Maele, G., Therasse, P., Lenoir, E., Desager, J.-P., Despontin, K., Gofflot, F., Jacobs, M.-C., Lecart, C., Berthet, P., Lachapelle, J.-M., & Picard, J. (1993). Embryotoxicity of human sera from patients treated with isotretinoin. Toxicology in Vitro, 7(6), 809-815. https://doi.org/10.1016/0887-2333(93)90085-J (Original work published 1993)