© 1989 Oxford University Press
research-article |
Target Tissue Morphology and Serum Biochemistry following 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Exposure in a TCDD-Susceptible and a TCDD-Resistant Rat Strain1
*Department of Environmental Hygiene and Toxicology. National Public Health Institute POB 95. SF- 70701 Kuopio. Finland
Department of Pathology. University of Kuopio Kuopio, Finland
Department of Histology and Cell Biology. University ofAmsterdam Amsterdam, The Netherlands
Department ofPharmacology and Toxicology, University of Helsinki Helsinki, Finland
#Department of Pharmacology and Toxicology. University of Kuopio Kuopio, Finland
||Department of Pharmacology, Toxicology and Therapeutics. University of Kansas Medical Center Kansas City, Kansas 66103
Received March 22, 1988; accepted December 9, 1988
Target Tissue Morphology and Serum Biochemistry following 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Exposure in a TCDD-Susceptible and a TCDD-Resistant Rat Strain. POHJANVIRTA, R., KULJU, T., MORSELT, A. F. W., TUOMINEN, R., JUVONEN, R., ROZMAN, K.,MÄNNISTÖ, P., COLLAN, Y., SAINIO, E.-L., AND TUOMISTO, J. (1989). Fundam. Appl. Toxicol. 12, 698–712. The mode of action of the highly toxic environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is unknown. It was recently discovered that two strains of rat, Long-Evans (L-E) and Han/Wistar (H/W), differ widely in susceptibility to TCDD. Employing this strain divergence as a probe, the present study set out to assess the role of various biochemical and morphological effects in TCDD lethality. In the main experiment, the rats were treated once ip with 0, 5, 50, or (H/W) 500 µg/kg TCDD and killed 1 to 16 days postexposure. Several target organs were evaluated by light microscopy and a number of serum lipid and carbohydrate parameters as well as a few major regulatory hormones were analyzed. The results demonstrated that most alterations caused by TCDD were essentially similar in both strains. TCDD reduced circulating thyroxine to a slightly greater extent and more permanently in the sensitive L-E strain. Moreover, a highly significant interaction on thyroid-stimulating hormone was found among strain, dose. and time. Serum concentrations of corticosterone and free fatty acids were increased only in the L-E rats given 50 µg/kg TCDD, i.e., at an apparent LDl00 dose level for this strain. Yet, the most striking interstrain difference was seen in the liver which was distinctly affected after Day 4 in L-E rats given 50 µg/kg TCDD but only marginally affected in rats from any H/W group. The lesion, while showing no necrotic cell changes, was suggestive of plasma membrane damage, possibly reflecting the production of free radicals. The relation of the findings to possible mechanisms of TCDD action is discussed.