2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) INDUCED ETHOXYRESORUFIN-O-DEETHYLASE (EROD) AND ALDEHYDE DEHYDROGENASE (ALDH3) ACTIVITIES IN THEBRAIN AND LIVER - A COMPARISON BETWEEN THE MOST TCDD-SUSCEPTIBLE AND THE MOST TCDD-RESISTANT RAT STRAIN

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent inducer of etho xyresorufin O-deethylase (EROD) and aldehyde dehydrogenase (EC 1.2.1.3 ., ALDH3) enzyme activities in the liver. Little is known about their inducibility by TCDD in the brain, although it may be a target organ f or TCDD toxicity. Two strains of rat, Long-Evans (L-E) and Han/Wistar (H/W) exhibit an over 1000-fold difference in their LD50-values for TC DD. The induction of EROD and ALDH3 in discrete brain regions and in t he liver of L-E and H/W rats were now compared at 10 days after TCDD e xposure to assess the role of these responses in the strain difference . Liver EROD and ALDH, were maximally induced at 5 mug/kg and 50 mug/k g, respectively, in both strains. In the brain 50 mug/kg TCDD was most ly needed to enhance EROD activity in both strains. The induction occu rred especially in olfactory bulbs, but was also seen in the midbrain plus thalamus of both rat strains. The induced EROD activity in the ol factory bulb was almost totally abolished by a monoclonal antibody (Ma b) 1-7-1 raised against CYP1A1. ALDH3 activities were increased more d ose dependently in olfactory bulbs of H/W than L-E rats. In other brai n areas measured, ALDH3 activities were induced more in L-E rats. Kine tic factors did not explain the differential induction of EROD and ALD H3 among discrete brain regions. We conclude that both EROD and ALDH3 are induced in the brain by TCDD although the activities are much lowe r than in the liver. The induction in the brain is region specific wit h olfactory bulbs being the most responsive area. As in the liver, the TCDD-induced activity of EROD in the brain is primarily associated wi th CYP1A1. According to the present findings, enzyme induction in the brain does not seem to have a crucial role in determining the strain s usceptibility to the acute lethality of TCDD.