Chick embryo chorioallantoic membrane (CAM): an alternative predictive model in acute toxicological studies for anti-cancer drugs.
The chick embryo chorioallantoic membrane (CAM) is a preclinical model widely used for vascular and anti-vascular effects of therapeutic agents in vivo. In this study, we examine the suitability of CAM as a predictive model for acute toxicology studies of drugs by comparing it to conventional mouse and rat models for 10 FDA-approved anticancer drugs (paclitaxel, carmustine, camptothecin, cyclophosphamide, vincristine, cisplatin, aloin, mitomycin C, actinomycin-D, melphalan). Suitable formulations for intravenous administration were determined before the average of median lethal dose (LD50) and median survival dose (SD(50)) in the CAM were measured and calculated for these drugs. The resultant ideal LD(50) values were correlated to those reported in the literature using Pearson's correlation test for both intravenous and intraperitoneal routes of injection in rodents. Our results showed moderate correlations (r(2)=0.42 - 0.68, P<0.005-0.05) between the ideal LD(50) values obtained using the CAM model with LD(50) values from mice and rats models for both intravenous and intraperitoneal administrations, suggesting that the chick embryo may be a suitable alternative model for acute drug toxicity screening before embarking on full toxicological investigations in rodents in development of anticancer drugs.
Cancer Research Initiative Foundation (CARIF), Sime Darby Medical Centre, 47500 Subang Jaya, Selangor, Malaysia.
Chin Siang
CS
Kue
Kae Yi
KY
Tan
May Lynn
ML
Lam
Hong Boon
HB
Lee
D000826:Animal Testing Alternatives / Q000379:methods*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D051379:Mice; D023421:Models, Animal; D051381:Rats; D023382:Toxicity Tests, Acute / Q000379:methods*
D000970:Antineoplastic Agents