Teratogenesis and inhibition of DNA synthesis induced in rat embryos by cytosine arabinoside.

  title={Teratogenesis and inhibition of DNA synthesis induced in rat embryos by cytosine arabinoside.},
  author={E. J. Ritter and William J. Scott and J. Gerald Wilson},
  volume={4 1},
Pregnant Wistar rats were injected at day 12 of gestation with 25, 50, 100, or 200 mg/kg cytosine arabinoside. One to 27 hours later 3H-thymidine was also injected followed 2 hours later by surgical removal of one uterine horn. The remaining horn was left in situ until day 20 for evaluation of embryotoxicity (malformation, death, or growth retardation). Half of the embryos in the removed horn were prepared individually for whole-embryo scintillation counts and the other half were homogenized… 
DNA synthesis inhibition, cytotoxicity and their relationship to teratogenesis following administration of a nicotinamide antagonist, aminothiadiazole, to pregnant rats.
It is proposed that the time of appearance of maximal cell death plays a major role in determining the degree and pattern of forelimb ectrodactyly, especially in the limb buds and neural tube.
Teratogenic effects of the pyrimidine analogues 5‐lododeoxyuridine and cytosine arabinoside in late fetal mice and rats
Pregnant mice and rats were treated daily with 5-iododeoxyuridine (IUDR) or cytosine arabinoside (CA) on 3 consecutive days, beginning on day 16 and 18 of pregnancy, respectively. Offspring were
Incorporation of 5-lododeoxyuridine into the DNA of mouse embryos: its relation to embryotoxicity.
Growth of embryos following injection on day 10 resulted in decreased 3H-specific activity in the DNA fraction and concomitant retention of total activity, suggesting that the previously demonstrated embryotoxicity of IdU is related to its retention at its presumed intracellular site of action.
Effects of cytosine arabinoside on in vivo and in vitro mouse limb development
Production of this morphologically distinct malformation in vitro will allow detailed biochemical investigations on the effect of ara-C limb ectodermal-mesenchymal interactions.
Effects of cytosine arabinoside on rat and rabbit embryos cultured in vitro.
Cellular and biochemical aspects of growth retardation in rat fetuses induced by maternal administration of selected anticancer agents.
Differences in DNA, RNA, and protein are believed to be related to drug-induced growth retardation incident to total fetal DNA reduction resulting in diminished cell number.
Limb development in mouse embryos. II. Reduction defects, cytotoxicity and inhibition of DNA synthesis produced by cytosine arabinoside.
Various morphological and biochemical parameters were used to study the mode of interference by cytosine arabinoside (Ara-C) in critical phases of embryonic limb development, finding that there may be a common cellular basis underlying these two types of digital defects.
Maternal and developmental toxicity of low doses of cytosine arabinoside in mice.
The developmental no-observed-adverse-effect-level (NOAEL) of Ara-C in the pregnant mouse is lower than 0.5 mg/kg/day, while the NOAEL for maternal toxicity is 0.1-beta-D-Arabinofuranosylcytosine (Ara-C).


The data presented in this communication taken together with observations of other workers would appear to suggest that the effect of the drug may be directly on the DNA molecule, and can be partially prevented by the addition of deoxyribonucleosides which in sufficient concentration appear to compete temporarily with the drug.
Megaloblastosis Produced by a Cytosine Antagonist
1. Cytosine arabinoside induced objective, but temporary, decrease of tumor masses in three patients with lymphosarcoma and slight decrease in some lesions in two out of ten treated patients with
Antitumor Activity of 1-β-D-Arabinofuranosylcytosine Hydrochloride
Summary 1-β-D-Arabinofuranosylcytosine hydrochloride has been shown to be active against recently transplanted and established Sarcoma 180, Ehrlich carcinoma and L-1210 leukemia in mice. This