Characterization of cardiotoxicity induced by 2,3,7, 8-tetrachlorodibenzo-p-dioxin and related chemicals during early chick embryo development.
Cardiotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was studied in White Leghorn-Babcock (WLB) and Plymouth Rock-Barred (PRB) chick embryos. TCDD, injected on day 0 (D0), induced a dose-related increase in heart weight in both strains in the absence of pericardial edema on D10. PRB embryos were four to five times more sensitive to this cardiotoxicity than WLB. To determine if another aryl hydrocarbon receptor agonist produced a similar response, graded doses of TCDD; 3,3',4,4',5-pentachlorobiphenyl (PeCB 126); or 2,2',4,4',5,5'-hexachlorobiphenyl (HxCB 153) were injected into WLB eggs. TCDD and PeCB 126 induced a dose-related increase in heart weight without pericardial edema, while HxCB 153 had no effect. We then hypothesized that TCDD-induced cardiotoxicity progressed to heart failure and edema. In PRB, morphometric analysis revealed that TCDD (0.06-0.45 pmol/g) induced a dose-related increase in left and right ventricle cavity area without wall hypertrophy on D10, consistent with dilated cardiomyopathy. A time course showed that 0.24 pmol/g did not alter heart morphology on D8 but induced cardiac dilation on D10 and D12. The 0.24 pmol/g dose also induced changes associated with progression of cardiomyopathy toward heart failure, including increased cardiac atrial natriuretic factor mRNA expression and decreased cardiac responsiveness to isoproterenol-induced positive chronotropy, on D10 and D12. Finally, 0.24 pmol/g induced a significantly higher incidence of subcutaneous and peritoneal edema, indicative of overt heart failure, on D12 (75%, 15/20) compared to D10 (14%, 3/22). In conclusion, TCDD induced a phenotype of dilated cardiomyopathy and symptoms associated with the development of congestive heart failure.
Walker
M K
MK
College of Pharmacy, University of New Mexico, Albuquerque, New Mexico 87131, USA. mkwalker@unm.edu
Catron
T F
TF
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D015152:Blotting, Northern; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000502:physiology; D004785:Environmental Pollutants / Q000633:toxicity*; D006321:Heart / Q000187:drug effects* / Q000196:embryology / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000633:toxicity; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity
D000199:Actins; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D009320:Atrial Natriuretic Factor; D011078:Polychlorinated Biphenyls; D007545:Isoproterenol; C023035:3,4,5,3',4'-pentachlorobiphenyl; C014024:2,4,5,2',4',5'-hexachlorobiphenyl