PMID- 16300371
OWN - NLM
STAT- MEDLINE
DCOM- 20060118
LR  - 20071114
IS  - 0893-228X (Print)
IS  - 0893-228X (Linking)
VI  - 18
IP  - 11
DP  - 2005 Nov
TI  - Effects of 3-methylcholanthrene on gene expression profiling in the rat using 
      cDNA microarray analyses.
PG  - 1634-41
AB  - There is significant human exposure to polycyclic aromatic hydrocarbons (PAHs), 
      many of which are bioactivated by the cytochrome P450 (P450) 1A family of enzymes 
      to metabolites that are capable of covalently binding to DNA, a critical step in 
      the initiation of carcinogenesis. We reported earlier that exposure of rats to 
      3-methylcholanthrene (MC) causes sustained induction of hepatic cytochrome P4501A 
      expression for up to 45 days. Here, we tested the hypothesis that MC elicits 
      persistent induction of other genes that are regulated by the Ah receptor (AHR). 
      Female Sprague-Dawley rats were treated with MC (100 micromol/kg) ip once daily 
      for 4 days, and gene expression patterns were investigated using total liver RNA 
      isolated from animals at 1, 15, and 28 days after MC withdrawal. Gene expression 
      was studied by cDNA microarray analyses using 4608 unique clones from 
      liver-derived expressed sequence tag (EST) libraries fortified with clones of 
      known liver genes representing approximately 4000 genes. Several phase I 
      (P4501A1, -1A2) and phase II [e.g., glutathione-S-transferase (GST)-M1, 
      UDP-glucuronosyl transferases (UGT)] genes were persistently induced (3-10-fold) 
      by MC for 15-28 days. The persistent induction of P4501A1 gene expression was 
      confirmed by real time reverse transcriptase polymerase chain reaction (RT-PCR) 
      experiments. MC also elicited a 5-fold persistent augmentation of acute phase 
      genes such as orosomucoid 1 and alpha-1-acid glycoprotein (AGP), and this was 
      accompanied by sustained liver damage and inflammation in the MC-exposed rats. In 
      conclusion, our results strongly suggest that sustained induction of P4501A1 by 
      MC is accompanied by persistent expression of other genes belonging to the Ah 
      gene battery, as well as certain other genes involved in toxic responses. 
      Elucidating the mechanisms of persistent induction of P4501A1 and other genes by 
      MC might lead to a better understanding of the mechanisms of toxicity mediated by 
      PAHs.
FAU - Kondraganti, Sudha R
AU  - Kondraganti SR
AD  - Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
FAU - Muthiah, Kathirvel
AU  - Muthiah K
FAU - Jiang, Weiwu
AU  - Jiang W
FAU - Barrios, Roberto
AU  - Barrios R
FAU - Moorthy, Bhagavatula
AU  - Moorthy B
LA  - eng
GR  - 2R01 ES009132/ES/NIEHS NIH HHS/United States
GR  - R01 HL070921/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (Acute-Phase Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 56-49-5 (Methylcholanthrene)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
SB  - IM
MH  - Acute-Phase Proteins/genetics
MH  - Animals
MH  - Cytochrome P-450 CYP1A1/genetics
MH  - *Gene Expression Profiling
MH  - Gene Expression Regulation/*drug effects
MH  - Glucuronosyltransferase/genetics
MH  - Liver/drug effects/metabolism/pathology
MH  - Male
MH  - Methylcholanthrene/*toxicity
MH  - *Oligonucleotide Array Sequence Analysis
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Aryl Hydrocarbon/genetics
EDAT- 2005/11/23 09:00
MHDA- 2006/01/19 09:00
CRDT- 2005/11/23 09:00
PHST- 2005/11/23 09:00 [pubmed]
PHST- 2006/01/19 09:00 [medline]
PHST- 2005/11/23 09:00 [entrez]
AID - 10.1021/tx050085n [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2005 Nov;18(11):1634-41. doi: 10.1021/tx050085n.