PMID- 12167210
OWN - NLM
STAT- MEDLINE
DCOM- 20020919
LR  - 20131121
IS  - 1528-7394 (Print)
IS  - 0098-4108 (Linking)
VI  - 65
IP  - 17
DP  - 2002 Sep 13
TI  - Effect of mercury vapor exposure on metallothionein and glutathione s-transferase 
      gene expression in the kidney of nonpregnant, pregnant, and neonatal rats.
PG  - 1273-88
AB  - Elemental mercury (Hg(0)) is a ubiquitous toxic pollutant. Exposure to Hg(0) 
      vapor typically is by inhalation, and the kidney is the primary target organ. 
      Glutathione (GSH) and metallothionein (MT) appear to mitigate mercury toxicity. 
      However, little is known about GSH or MT regulation after Hg(0) vapor exposure, 
      particularly during pregnancy, a time of high sensitivity to most metals. Thus, 
      this study sought to determine renal mercury accumulation and MT- and GSH-related 
      gene expression following Hg(0) vapor exposure in nonpregnant, pregnant, and 
      neonatal rats exposed in utero. Groups (n = 5) of pregnant rats (Long-Evans) were 
      exposed to Hg(0) vapor (4 mg/m(3)) or air (control) for 2 h/d from gestational 
      day (GD) 6 to 15, and kidneys from dams and pups were removed at various times 
      during and after the onset of exposure. For comparative purposes, nonpregnant 
      female rats were exposed to Hg(0) for 10 d under the same conditions. Renal 
      mercury, MT protein, and GST activity were assayed by standard analytical 
      techniques. Western blot analysis was also performed using antibodies against MT 
      and GST-pi. GSH-related gene expression was studied by cDNA microarray. Hg(0) 
      vapor exposure produced renal accumulation of mercury in nonpregnant, pregnant, 
      and neonatal rats. However, the transplacentally exposed neonates accumulated 
      approximately 1000-fold less mercury than adults. Hg(0) vapor exposure produced a 
      time-dependent increase in renal MT protein in nonpregnant and pregnant rats, but 
      not in neonatal rats. Maximum MT increases were observed on d 10 (fivefold) in 
      nonpregnant and GD 15 (threefold) in pregnant rats. Activation of the MT gene by 
      Hg(0) was confirmed at the translational level by Western blot analysis and at 
      the transcriptional level by Northern blot analysis. Microarray analysis revealed 
      a significant upregulation in the renal expression of the GST-pi, GST-Ya, and 
      microsomal GST and GST5-5 genes in nonpregnant and pregnant rats. Western blot 
      and enzyme assay confirmed the upregulation of GST genes after Hg(0) exposure. 
      Thus, in response to Hg(0) vapor exposure, the expression of the MT gene and 
      various GST genes is activated in nonpregnant and pregnant rats. Activation of 
      these genes could be part of a defensive response directed at decreasing renal 
      mercury toxicity, and may help divert the metal away from the fetus.
FAU - Brambila, Eduardo
AU  - Brambila E
AD  - Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, 
      National Cancer Institute at National Institute of Environmental Health Sciences, 
      Research Triangle Park, North Carolina 27709, USA.
FAU - Liu, Jie
AU  - Liu J
FAU - Morgan, Daniel L
AU  - Morgan DL
FAU - Beliles, Robert P
AU  - Beliles RP
FAU - Waalkes, Michael P
AU  - Waalkes MP
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - J Toxicol Environ Health A
JT  - Journal of toxicology and environmental health. Part A
JID - 100960995
RN  - 9038-94-2 (Metallothionein)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - FXS1BY2PGL (Mercury)
SB  - IM
MH  - Administration, Inhalation
MH  - Animals
MH  - Animals, Newborn/*physiology
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Female
MH  - Gene Expression Regulation, Enzymologic/*genetics
MH  - Glutathione Transferase/*biosynthesis/genetics
MH  - Kidney/*enzymology/metabolism
MH  - Mercury/metabolism/*toxicity
MH  - Metallothionein/*biosynthesis/genetics
MH  - Oligonucleotide Array Sequence Analysis
MH  - Pregnancy
MH  - Pregnancy, Animal/*genetics
MH  - Rats
MH  - Rats, Long-Evans
EDAT- 2002/08/09 10:00
MHDA- 2002/09/20 10:01
CRDT- 2002/08/09 10:00
PHST- 2002/08/09 10:00 [pubmed]
PHST- 2002/09/20 10:01 [medline]
PHST- 2002/08/09 10:00 [entrez]
AID - 10.1080/152873902760125750 [doi]
PST - ppublish
SO  - J Toxicol Environ Health A. 2002 Sep 13;65(17):1273-88. doi: 
      10.1080/152873902760125750.