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

Abstract 2,3,7,8-Tetrachlorodibenzo- p -dioxin (TCDD) is a potent inducer of ethoxyresorufin O -deethylase (EROD) and aldehyde dehydrogenase (EC 1.2.1.3., ALDH 3 ) enzyme activities in the liver. Little is known about their inducibility by TCDD in the brain, although it may be a target organ for TCDD toxicity. Two strains of rat, Long-Evans (L-E) and Han/Wistar (H/W) exhibit an over 1000-fold difference in their ld 50 -values for TCDD. The induction of EROD and ALDH 3 in discrete brain regions and in the liver of L-E and H/W rats were now compared at 10 days after TCDD exposure to assess the role of these responses in the strain difference. Liver EROD and ALDH 3 were maximally induced at 5 μg/kg and 50 μg/kg, respectively, in both strains. In the brain 50 μg/kg TCDD was mostly needed to enhance EROD activity in both strains. The induction occurred especially in olfactory bulbs, but was also seen in the midbrain plus thalamus of both rat strains. The induced EROD activity in the olfactory bulb was almost totally abolished by a monoclonal antibody (Mab) 1-7-1 raised against CYP1A1. ALDH 3 activities were increased more dose dependently in olfactory bulbs of H/W than L-E rats. In other brain areas measured, ALDH 3 activities were induced more in L-E rats. Kinetic factors did not explain the differential induction of EROD and ALDH 3 among discrete brain regions. We conclude that both EROD and ALDH 3 are induced in the brain by TCDD although the activities are much lower than in the liver. The induction in the brain is region specific with olfactory bulbs being the most responsive area. As in the liver, the TCDD-induced activity of EROD in the brain is primarily associated with CYP1A1. According to the present findings, enzyme induction in the brain does not seem to have a crucial role in determining the strain susceptibility to the acute lethality of TCDD.