Taxol and embryonic development in the chick.
Taxol, an inhibitor of microtubule disassembly, is currently under investigation in the therapy of several human cancers. The current investigation was undertaken to characterize potential taxol developmental toxicity in chicks. On one of days 1-4 of incubation, taxol was administered in dimethylsulfoxide (DMSO) or olive oil in a range of doses, the highest of which produced a high incidence of early embryo death. Production of gross structural malformations was sporadic and occurred in vehicle-treated as well as taxol-treated embryos. A more common manifestation of taxol toxicity was a syndrome of visceral abnormalities, including regression of the vitelline circulation, dilatation of the atria, and hemorrhage in the left side of the head and thorax, often with decreased eye pigmentation. Regardless of the day of treatment, this syndrome occurred at 4.5-5 days. To investigate the possibility that taxol induced its effect through disruption of angiogenesis in the vitelline circulation, filters soaked in taxol were applied to the margin of the germ disc. No inhibition of vessel development was demonstrated. We conclude that taxol decreases the viability of embryos and that this impairment of survival precludes the development of birth defects. Solvent toxicity is an important confounder in the investigation of taxol embryotoxicity.
Scialli
A R
AR
Department of Obstetrics and Gynecology, Georgetown University Medical Center, Washington, D.C. 20007-2197.
DeSesso
J M
JM
Goeringer
G C
GC
D000014:Abnormalities, Drug-Induced; D000818:Animals; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D009389:Neovascularization, Pathologic / Q000139:chemically induced; D017239:Paclitaxel / Q000633:toxicity*; D013997:Time Factors
D017239:Paclitaxel