A chick model for the mechanisms of mustard gas neurobehavioral teratogenicity.
The chemical warfare blistering agent, sulfur mustard (SM), is a powerful mutagen and carcinogen. Due to its similarity to the related chemotherapy agents nitrogen mustard (mechlorethamine), it is expected to act as a developmental neurotoxicant. The present study was designed to establish a chick model for the mechanisms of SM on neurobehavioral teratogenicity, free of confounds related to mammalian maternal effects. Chicken eggs were injected with SM at a dose range of 0.0017-17.0 microg/kg of egg, which is below the threshold for dysmorphology, on incubation days (ID) 2 and 7, and then tests were conducted posthatching. Exposure to SM elicited significant deficits in the intermedial part of the hyperstriatum ventrale (IMHV)-related imprinting behavior. Parallel decreases were found in the level of membrane PKCgamma in the IMHV, while eliciting no net change in cytosolic PKCgamma. The chick, thus, provides a suitable model for the rapid evaluation of SM behavioral teratogenicity and elucidation of the mechanisms underlying behavioral anomalies. The results obtained, using a model that controls for confounding maternal effects, may be replicated in the mammalian model and provide the groundwork for studies designed to offset or reverse the SM-induced neurobehavioral defects in both avian and mammals.
Wormser
Uri
U
Department of Pharmacology, School of Pharmacy, Faculty of Medicine, Institute of Life Sciences, The Hebrew University, Jerusalem, Israel.
Izrael
Michal
M
Van der Zee
Eddy A
EA
Brodsky
Berta
B
Yanai
Joseph
J
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D002552:Cerebral Ventricles / Q000378:metabolism; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002642:Chick Embryo; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D005260:Female; D007173:Imprinting, Psychological / Q000187:drug effects; D008466:Mechlorethamine / Q000633:toxicity*; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D013997:Time Factors
D002619:Chemical Warfare Agents; D008466:Mechlorethamine; C087857:protein kinase C gamma; D011493:Protein Kinase C