TAXOL AND EMBRYONIC-DEVELOPMENT IN THE CHICK

Taxol, an inhibitor of microtubule disassembly, is currently under inv estigation in the therapy of several human cancers. The current invest igation was undertaken to characterize potential taxol developmental t oxicity in chicks. On one of days 1-4 of incubation, taxol was adminis tered in dimethylsulfoxide (DMSO) or olive oil in a range of doses, th e highest of which produced a high incidence of early embryo death. Pr oduction of gross structural malformations was sporadic and occurred i n vehicle-treated as well as taxol-treated embryos. A more common mani festation of taxol toxicity was a syndrome of visceral abnormalities, including regression of the vitelline circulation, dilatation of the a tria, and hemorrhage in the left side of the head and thorax, often wi th decreased eye pigmentation. Regardless of the day of treatment, thi s syndrome occurred at 4.5-5 days. To investigate the possibility that taxol induced its effect through disruption of angiogenesis in the vi telline circulation, filters soaked in taxol were applied to the margi n of the germ disc. No inhibition of vessel development was demonstrat ed. We conclude that taxol decreases the viability of embryos and that this impairment of survival precludes the development of birth defect s. Solvent toxicity is an important confounder in the investigation of taxol embryotoxicity. (C) 1994 Wiley-Liss, Inc.