PMID- 18203689
OWN - NLM
STAT- MEDLINE
DCOM- 20080410
LR  - 20240323
IS  - 1096-0929 (Electronic)
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 102
IP  - 2
DP  - 2008 Apr
TI  - Persistent induction of hepatic and pulmonary phase II enzymes by 
      3-methylcholanthrene in rats.
PG  - 337-44
LID - 10.1093/toxsci/kfn007 [doi]
AB  - We reported earlier that exposure of rats to 3-methylcholanthrene (MC) causes 
      sustained induction of hepatic cytochrome P450 (CYP)1A expression for up to 45 
      days by mechanisms other than persistence of the parent MC (Moorthy, J. 2000. 
      Pharmacology. Exp. Ther. 294, 313-322). The CYP1A genes are members of the Ah 
      gene battery that also encode CYP1B1 and phase II enzymes such as glutathione 
      S-transferase (GST-alpha), UDP glucuronyl transferase (UGT)1A, NAD(P)H 
      (nicotinamide adenine dinucleotide phosphate, reduced):quinone oxidoreductase I 
      (NQO1), aldehyde dehydrogenase (ALDH), etc. Therefore, in this investigation, we 
      tested the hypothesis that MC elicits persistent induction of CYP1B1 and phase II 
      genes, which are in part regulated by the Ah receptor (AHR). Female 
      Sprague-Dawley rats were treated with MC (100 mumol/kg), ip, once daily for 4 
      days, and expression of CYP1B1 and several phase II (e.g., GST-alpha, NQO1) genes 
      and their corresponding proteins were determined in lung and liver. The major 
      finding was that MC persistently induced (3- to 10-fold) the expression of 
      several phase II enzymes, including GST-alpha, NQO1, UGT1A1, ALDH, and epoxide 
      hydrolase in both tissues for up to 28 days. However, MC did not elicit sustained 
      induction of CYP1B1. Our results thus support the hypothesis that MC elicits 
      coordinated and sustained induction of phase II genes presumably via persistent 
      activation of the AHR, a phenomenon that may have implications for 
      chemical-induced carcinogenesis and chemopreventive strategies in humans.
FAU - Kondraganti, Sudha R
AU  - Kondraganti SR
AD  - Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030.
FAU - Jiang, Weiwu
AU  - Jiang W
FAU - Jaiswal, Anil K
AU  - Jaiswal AK
FAU - Moorthy, Bhagavatula
AU  - Moorthy B
LA  - eng
GR  - R01 ES009132/ES/NIEHS NIH HHS/United States
GR  - R01 ES07943/ES/NIEHS NIH HHS/United States
GR  - R01ES009132/ES/NIEHS NIH HHS/United States
GR  - R01HL070921/HL/NHLBI NIH HHS/United States
GR  - R01HL087174/HL/NHLBI NIH HHS/United States
GR  - R01 HL070921/HL/NHLBI NIH HHS/United States
GR  - R01 ES007943/ES/NIEHS NIH HHS/United States
GR  - R01 HL087174/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20080117
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Carcinogens)
RN  - 0 (Isoenzymes)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Ugt1a1 protein, rat)
RN  - 56-49-5 (Methylcholanthrene)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
RN  - EC 1.14.14.1 (CYP1B1 protein, human)
RN  - EC 1.14.14.1 (Cyp1b1 protein, rat)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1B1)
RN  - EC 1.2.1.3 (Aldehyde Dehydrogenase)
RN  - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone))
RN  - EC 1.6.5.2 (NQO1 protein, rat)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - EC 2.5.1.18 (glutathione S-transferase alpha)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
SB  - IM
MH  - Aldehyde Dehydrogenase/biosynthesis/genetics
MH  - Animals
MH  - Aryl Hydrocarbon Hydroxylases/biosynthesis/genetics
MH  - Carcinogens/*toxicity
MH  - Cytochrome P-450 CYP1B1
MH  - Enzyme Induction/drug effects
MH  - Epoxide Hydrolases/biosynthesis/genetics
MH  - Female
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Glucuronosyltransferase/biosynthesis/genetics
MH  - Glutathione Transferase/biosynthesis/genetics
MH  - Injections, Intraperitoneal
MH  - Isoenzymes/biosynthesis/genetics
MH  - Liver/*drug effects/enzymology
MH  - Lung/*drug effects/enzymology
MH  - Metabolic Detoxication, Phase II/*physiology
MH  - Methylcholanthrene/*toxicity
MH  - Microsomes, Liver/drug effects/enzymology
MH  - NAD(P)H Dehydrogenase (Quinone)/biosynthesis/genetics
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Aryl Hydrocarbon/genetics/metabolism
PMC - PMC3758893
MID - NIHMS494421
EDAT- 2008/01/22 09:00
MHDA- 2008/04/11 09:00
PMCR- 2013/09/01
CRDT- 2008/01/22 09:00
PHST- 2008/01/22 09:00 [pubmed]
PHST- 2008/04/11 09:00 [medline]
PHST- 2008/01/22 09:00 [entrez]
PHST- 2013/09/01 00:00 [pmc-release]
AID - kfn007 [pii]
AID - 10.1093/toxsci/kfn007 [doi]
PST - ppublish
SO  - Toxicol Sci. 2008 Apr;102(2):337-44. doi: 10.1093/toxsci/kfn007. Epub 2008 Jan 
      17.