PMID- 15893545
OWN - NLM
STAT- MEDLINE
DCOM- 20050707
LR  - 20141120
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 205
IP  - 2
DP  - 2005 Jun 1
TI  - Accumulation of methylmercury or polychlorinated biphenyls in in vitro models of 
      rat neuronal tissue.
PG  - 177-87
AB  - In vivo exposure levels for neurotoxicants are often reported in parts per 
      million (ppm) concentration in tissue, whereas exposure levels in experiments 
      utilizing in vitro models are most commonly reported in micromolar (muM) 
      concentration in the exposure solution. The present experiments sought to 
      determine whether or not in vitro solution concentration was an appropriate 
      dose-metric for comparison to in vivo tissue levels for lipophilic compounds. To 
      do so, the accumulation of the polychlorinated biphenyl (PCB) mixture Aroclor 
      1254 (A1254) or methylmercury (MeHg) was examined in three commonly utilized in 
      vitro neuronal tissue models: nerve growth factor differentiated pheochromocytoma 
      (PC12) cells, primary cultures of rat neocortical cells, and adult rat 
      hippocampal slices. Tissues were exposed to A1254 (0.65 ppm) or to MeHg 
      (0.0033-0.33 ppm) in serum-free media for 1 or 24 h. Total PCB or mercury 
      accumulation was measured by dual column gas chromatography with electron capture 
      detection or by cold vapor atomic absorption, respectively. PC12 cells 
      accumulated 66.7 and 103.8 ppm PCBs after 1 and 24 h exposure to A1254. 
      Neocortical neurons also accumulated significant concentrations of PCBs, but less 
      so than PC12 cells. After 1 h exposure to 0.65 ppm A1254, slices contained 3.46 
      and 0.81 ppm PCBs when exposed in a static and perfused system, respectively. 
      After 1 h exposure to 0.0033, 0.033, and 0.33 ppm MeHg, PC12 cells contained 0.3, 
      2.2, and 17.7 ppm mercury, respectively; after 24 h, PC12 cells contained 0.4, 
      2.8, and 21.9 ppm. Hippocampal slices accumulated 1.7 and 4.8 ppm mercury after 1 
      and 3 h exposure to 0.33 ppm MeHg. For comparison, mercury accumulation in rat 
      fetal and pup brain tissue after maternal exposure [0, 0.1, 1.0, or 2.0 mg/kg/day 
      MeHg from gestational day (GD) 6-15] ranged from 0.05 to 7.89 ppm in 0.1 mg/kg 
      dose animals on postnatal day 10 and 2.0 mg/kg dose animals on GD16, 
      respectively. These results demonstrate that accumulation of PCBs and MeHg in 
      vitro is tissue-, time-, and concentration-dependent and indicates that tissue 
      levels rather than exposure concentrations are a more appropriate metric for 
      comparison of in vitro to in vivo effects.
FAU - Meacham, C A
AU  - Meacham CA
AD  - Neurotoxicology Division, National Health and Environmental Effects Research 
      Laboratory/ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 
      27711, USA.
FAU - Freudenrich, T M
AU  - Freudenrich TM
FAU - Anderson, W L
AU  - Anderson WL
FAU - Sui, L
AU  - Sui L
FAU - Lyons-Darden, T
AU  - Lyons-Darden T
FAU - Barone, S Jr
AU  - Barone S Jr
FAU - Gilbert, M E
AU  - Gilbert ME
FAU - Mundy, W R
AU  - Mundy WR
FAU - Shafer, T J
AU  - Shafer TJ
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20041119
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Culture Media)
RN  - 0 (Methylmercury Compounds)
RN  - 11097-69-1 (Chlorodiphenyl (54% Chlorine))
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Cells, Cultured
MH  - Chlorodiphenyl (54% Chlorine)/administration & dosage/*metabolism/toxicity
MH  - Culture Media
MH  - Dose-Response Relationship, Drug
MH  - Embryo, Mammalian/metabolism
MH  - Female
MH  - Hippocampus/*metabolism
MH  - In Vitro Techniques
MH  - Male
MH  - Maternal Exposure/adverse effects
MH  - Methylmercury Compounds/administration & dosage/*metabolism/toxicity
MH  - Models, Biological
MH  - Neocortex/*metabolism
MH  - PC12 Cells
MH  - Pregnancy
MH  - Rats
MH  - Rats, Long-Evans
MH  - Time Factors
EDAT- 2005/05/17 09:00
MHDA- 2005/07/08 09:00
CRDT- 2005/05/17 09:00
PHST- 2004/06/16 00:00 [received]
PHST- 2004/08/13 00:00 [revised]
PHST- 2004/08/17 00:00 [accepted]
PHST- 2005/05/17 09:00 [pubmed]
PHST- 2005/07/08 09:00 [medline]
PHST- 2005/05/17 09:00 [entrez]
AID - S0041-008X(04)00458-2 [pii]
AID - 10.1016/j.taap.2004.08.024 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2005 Jun 1;205(2):177-87. doi: 
      10.1016/j.taap.2004.08.024. Epub 2004 Nov 19.