An amphibian model to test the effects of xenobiotic chemicals on development of the hematopoietic system.

Abstract

A number of manmade chemicals have deleterious effects on the developing immune system. Very few assay systems are available to study the effects of xenobiotics on hematopoietic stem cells. In rodent models, assays require exposure of pregnant females and analysis of the hematopoietic potential of stem cells from the offspring. These models are less relevant to lower vertebrates such as fish or amphibians where exposure of embryos is direct. To overcome this problem, an amphibian model was developed. Diploid (2N) embryos (16-20 h of age) of the South African clawed frog, Xenopus laevis, were exposed to 10 microg/ml diazinon or 10(-6) M lead acetate for 2 h. After 2 h, the ventral blood island (VBI) was transplanted from a chemically treated or untreated control embryo to an untreated triploid (3N) host embryo. After 55 d, the contribution of the donor VBI-derived stem cells to populations in the blood, thymus, and spleen was assessed by flow cytometry. Diazinon, but not lead acetate, interfered with the ability of transplanted stem cells to contribute to hematopoiesis. Because amphibian embryos are very sensitive indicators of the toxic effects of chemicals, this VBI assay could be employed to test any toxic chemical that is suspected of having a negative effect on development of the hematopoietic system.