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Adriamycin effects on the chick embryo
A Mortell1, J Giles, J Bannigan
1The Children's Research Centre, Our Lady's Hospital for Sick Children, Crumlin, Dublin 12, Ireland.
Insights
This study investigated if Adriamycin causes VACTERL association anomalies in chick embryos, similar to the Adriamycin rat model. Researchers found no comparable developmental abnormalities, indicating chick embryos may not be a suitable model for VACTERL association research.
Area of Science:
- Developmental biology
- Teratology
- Pharmacology
Background:
- Adriamycin (chemotherapy drug) causes teratogenic effects in rats, mimicking human VACTERL association.
- The Adriamycin rat model (ARM) is used to study vertebral, anorectal, cardiac, tracheoesophageal, renal, and limb anomalies.
Purpose of the Study:
- To test if Adriamycin administration to chick embryos induces anomalies similar to the VACTERL association observed in the ARM.
- To evaluate chick embryos as a model for studying Adriamycin-induced developmental defects.
Main Methods:
- Fertilized Ross eggs received Adriamycin via air sac or albumin injection on days 0-3 of incubation.
- Embryos were analyzed on day 14 for morphological abnormalities, focusing on VACTERL-like defects.
- Control groups received saline injections.
Main Results:
- No chick embryos exhibited anomalies consistent with the VACTERL association.
- While some defects like ventral defects, anophthalmia, and exencephaly were observed, they did not replicate the ARM findings.
- Adriamycin administration showed varied survival rates and some non-specific developmental abnormalities in embryos.
Conclusions:
- Adriamycin administration to chick embryos does not replicate the VACTERL association anomalies seen in the Adriamycin rat model.
- Chick embryos may not be a suitable model for studying Adriamycin-induced VACTERL-like developmental defects.
- Different administration routes and timing did not yield comparable teratogenic effects.
Abstract:
Adriamycin is an anthracycline, anti-neoplastic drug with known teratogenic effects on foetal rats in what is known as the Adriamycin rat model (ARM). This includes conditions similar to those in newborn humans, known collectively as the VACTERL association. This comprises vertebral (V), anorectal (A), cardiac (C), tracheoesophageal (TE), renal (R) and limb (L) anomalies. We designed this study to test the hypothesis that the administration of Adriamycin to chick embryos would cause similar anomalies to those in the VACTERL association seen in the ARM. Fertilized Ross eggs received Adriamycin doses from 2-50 microg into the air sac and from 0.9-6 microg into the albumin. Administration varied from day 0-3 (D(0-3)) with D(0) being the first day of incubation. Control eggs received saline. Embryos were incubated at 38 degrees C and a relative humidity of 70%. Embryos were recovered on D(14), paraffin-embedded and transverse sections studied for morphological abnormalities. In the air sac group ( n=142), 71% of Adriamycin embryos survived versus 86% of controls (n=29). In the albumin group (n=121), 42% of Adriamycin embryos survived versus 55% of controls (n=69). No embryos demonstrated anomalies consistent with the VACTERL association. Ventral defects affected 1% of surviving Adriamycin embryos versus 4% of controls in the air sac group. In the albumin group, 19.8% of surviving Adriamycin embryos had ventral defects compared to 15.7% of surviving controls. Anophthalmia affected 1% of the surviving embryos in the Adriamycin air sac group and 2% of the Adriamycin albumin group. No controls developed anophthalmia. Exencephaly affected 2% of the survivors in the Adriamycin air sac group but none of the albumin group or controls. The administration of Adriamycin to chick embryos in comparable doses and times to those used in the ARM does not appear to produce comparable effects in relation to developmental anomalies, such as the VACTERL association. Despite examining different administration routes and mimicking the ARM, by giving Adriamycin to embryos at gastrulation, we were unable to re-create the anomalies seen in the ARM.