Adriamycin effects on the chick embryo.

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.