Congener-specific distribution of polychlorinated biphenyls in brain regions, blood, liver, and fat of adult rats following repeated exposure to Aroclor 1254

Our previous in vitro studies with both isolated organelles and primary neu ronal cell cultures found that intracellular signal transduction can be per turbed by some noncoplanar PCBs at exposure levels of less than or equal to 10 mu M. However, it is not clear whether such concentrations are achievab le in brain in vivo. Also, the pattern of congener disposition and quantiti es of the PCB accumulation in tissues of animals exposed to commercial PCB mixtures is not well studied. In the present study, we have conducted PCB c ongener-specific analysis in different brain regions, liver, blood, and fat of adult male Long-Evans rats dosed orally with Aroclor 1254 (0 or 30 mg/k g/day; once per day, 5 days/week for 4 weeks) in corn on. Twenty-four hours after the last dose, rats were euthanized, and the brains were removed and dissected to obtain cerebellum, frontal cortex, and striatum. Liver, blood , and fat samples were also collected at the same time. Congener-specific a nalysis of PCBs was performed by high-resolution gas chromatography with el ectron capture detection. While PCB concentrations in control rat brain reg ions were less than 0.02 ppm, total PCB congeners in treated animals accumu lated to much higher levels. Total levels in the frontal cortex, cerebellum , and striatum were 15.1 +/- 0.3, 13.1 +/- 1.7, and 8.2 +/- 2.6 ppm, respec tively. The levels of PCBs in the fat, liver, and blood were 0.041, 0.002, and 0.001 ppm in control rats and 552, 38.3, and 1.6 ppm in treated rats, r espectively. In addition to the differential total uptake between tissues, there was differential accumulation of PCBs with respect to the number of c hlorines. In all the tissues, the more lightly chlorinated (tetra- and pent a-) congeners accumulated less than their respective proportions in the par ent Aroclor 1254 mixture. On the other hand, heavily chlorinated (hexa- to nona-) congeners accumulated more than the proportion of these congeners fo und in Aroclor 1254 mixture. This shift toward accumulation of heavily chlo rinated congeners seems to be more pronounced in the brain than liver and f at. Predominant congeners (5-32% of total PCBs) detected in different brain regions, blood, liver, and fat are: 2,3,3',4',5,6- (no. 163)+ 2,2',3,4,4', 5- (no. 138)(coeluted); 2,2',4,4',5,5'- (no. 153)+ 2,2',3,3',4,6'- (no. 132 ) (coeluted); 2,3,3',4,4',5- (no. 156) + 2,2',3,3',4,4',6- (no. 171) (coelu ted); 2,3',4,4',5- (no. 118); 2,2',4,4',5-(no. 99); and 2,3,3',4,4'- (no. 1 05). These congeners together accounted for about two thirds of the total P CB load in brain. All these predominant congeners are ortho-substituted and therefore are noncoplanar in nature. The total PCB concentrations accumula ted in brain were as high as 50 mu M (based on average molecular weight of 326.4 for Aroclor 1254) and, at these concentrations, intracellular second messengers were significantly affected in neuronal cultures and brain homog enate preparations in vitro. These results indicate that concentrations tha t altered Ca2+ disposition and second messenger systems in vitro are achiev able in brain in vivo following repeated exposure, (C) 1998 Academic Press.