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

Target Tissue Morphology and Serum Biochemistry following 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) Exposure in a TCDD-Susceptible and a TCDD-Resistant RatStrain. 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 environmentalcontaminant 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 susceptibilityto TCDD. Employing this strain divergence as a probe, the presentstudy set out to assess the role of various biochemical andmorphological effects in TCDD lethality. In the main experiment,the rats were treated once ip with 0, 5, 50, or (H/W) 500 µg/kgTCDD and killed 1 to 16 days postexposure. Several target organswere evaluated by light microscopy and a number of serum lipidand carbohydrate parameters as well as a few major regulatoryhormones were analyzed. The results demonstrated that most alterationscaused by TCDD were essentially similar in both strains. TCDDreduced circulating thyroxine to a slightly greater extent andmore permanently in the sensitive L-E strain. Moreover, a highlysignificant interaction on thyroid-stimulating hormone was foundamong strain, dose. and time. Serum concentrations of corticosteroneand free fatty acids were increased only in the L-E rats given50 µg/kg TCDD, i.e., at an apparent LDl00 dose level forthis strain. Yet, the most striking interstrain difference wasseen in the liver which was distinctly affected after Day 4in L-E rats given 50 µg/kg TCDD but only marginally affectedin rats from any H/W group. The lesion, while showing no necroticcell changes, was suggestive of plasma membrane damage, possiblyreflecting the production of free radicals. The relation ofthe findings to possible mechanisms of TCDD action is discussed.