title: Congener-specific distribution of polychlorinated biphenyls in brain regions, blood, liver, and fat of adult rats following repeated exposure to Aroclor 1254.
abstract: Our previous in vitro studies with both isolated organelles and primary neuronal cell cultures found that intracellular signal transduction can be perturbed by some noncoplanar PCBs at exposure levels of </=10 microM. However, it is not clear whether such concentrations are achievable in brain in vivo. Also, the pattern of congener disposition and quantities 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 congener-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/kg/day; once per day, 5 days/week for 4 weeks) in corn oil. 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 analysis of PCBs was performed by high-resolution gas chromatography with electron capture detection. While PCB concentrations in control rat brain regions were less than 0.02 ppm, total PCB congeners in treated animals accumulated 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, respectively. 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, respectively. In addition to the differential total uptake between tissues, there was differential accumulation of PCBs with respect to the number of chlorines. In all the tissues, the more lightly chlorinated (tetra- and penta-) congeners accumulated less than their respective proportions in the parent Aroclor 1254 mixture. On the other hand, heavily chlorinated (hexa- to nona-) congeners accumulated more than the proportion of these congeners found in Aroclor 1254 mixture. This shift toward accumulation of heavily chlorinated congeners seems to be more pronounced in the brain than liver and fat. 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) (coeluted); 2,3',4,4',5- (no. 118); 2,2',4,4', 5-(no. 99); and 2,3,3',4,4'- (no. 105). These congeners together accounted for about two thirds of the total PCB load in brain. All these predominant congeners are ortho-substituted and therefore are noncoplanar in nature. The total PCB concentrations accumulated in brain were as high as 50 microM (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 homogenate preparations in vitro. These results indicate that concentrations that altered Ca2+ disposition and second messenger systems in vitro are achievable in brain in vivo following repeated exposure.
authors.affiliation: National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, 27711, USA.
authors.forename: P R
authors.initials: PR
authors.lastname: Kodavanti
authors.forename: T R
authors.initials: TR
authors.lastname: Ward
authors.forename: E C
authors.initials: EC
authors.lastname: Derr-Yellin
authors.forename: W R
authors.initials: WR
authors.lastname: Mundy
authors.forename: A C
authors.initials: AC
authors.lastname: Casey
authors.forename: B
authors.initials: B
authors.lastname: Bush
authors.forename: H A
authors.initials: HA
authors.lastname: Tilson
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D020111:Chlorodiphenyl (54% Chlorine) / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D002849:Chromatography, Gas; D003342:Corpus Striatum / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D011078:Polychlorinated Biphenyls / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D020318:Rats, Long-Evans; D015290:Second Messenger Systems / Q000187:drug effects*; D013997:Time Factors
chemical_list: D020111:Chlorodiphenyl (54% Chlorine); D011078:Polychlorinated Biphenyls; D002118:Calcium