PMID- 16049271
OWN - NLM
STAT- MEDLINE
DCOM- 20051207
LR  - 20161124
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 87
IP  - 2
DP  - 2005 Oct
TI  - Comparison of TCDD and PCB CYP1A induction sensitivities in fresh hepatocytes 
      from human donors, sprague-dawley rats, and rhesus monkeys and HepG2 cells.
PG  - 508-19
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related chemicals induce 
      cytochrome P450 1A (CYP1A) gene expression and, at sufficient exposures, cause 
      toxicity. Human health risks from such exposures are typically estimated from 
      animal studies. We tested whether animal models predict human sensitivity by 
      characterizing CYP1A gene expression in cultures of fresh hepatocytes from human 
      donors, rats, and rhesus monkeys and HepG2 human hepatoma cells. We exposed the 
      cells to three aryl hydrocarbon receptor (AhR) ligands of current environmental 
      interest and measured 7-ethoxyresorufin-O-deethylase (EROD) activity and 
      concentrations of CYP1A1 and CYP1A2 mRNA. We found that human cells are about 
      10-1000 times less sensitive to TCDD, 3,3',4,4',5-pentachlorobiphenyl (PCB 126), 
      and Aroclor 1254 than rat and monkey cells, that relative potencies among these 
      chemicals are different across species, and that gene expression thresholds exist 
      for these chemicals. Newly calculated rat-human interspecies relative potency 
      factors for PCB 126 were more than 100 times lower than the current 
      rodent-derived value. We propose that human-derived values be used to improve the 
      accuracy of estimates of human health risks.
FAU - Silkworth, Jay B
AU  - Silkworth JB
AD  - General Electric Company, Global Research Center, Niskayuna, New York 12309, USA. 
      silkworth@crd.ge.com
FAU - Koganti, Aruna
AU  - Koganti A
FAU - Illouz, Kati
AU  - Illouz K
FAU - Possolo, Antonio
AU  - Possolo A
FAU - Zhao, Ming
AU  - Zhao M
FAU - Hamilton, Stephen B
AU  - Hamilton SB
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050727
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Environmental Pollutants)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (RNA, Messenger)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A2)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Cytochrome P-450 CYP1A1/*biosynthesis
MH  - Cytochrome P-450 CYP1A2/*biosynthesis
MH  - Dose-Response Relationship, Drug
MH  - Environmental Pollutants/*toxicity
MH  - Enzyme Induction/drug effects
MH  - Hepatocytes/drug effects/*enzymology
MH  - Humans
MH  - Macaca mulatta
MH  - Polychlorinated Biphenyls/*toxicity
MH  - Polychlorinated Dibenzodioxins/*toxicity
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Species Specificity
EDAT- 2005/07/29 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/07/29 09:00
PHST- 2005/07/29 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/07/29 09:00 [entrez]
AID - kfi261 [pii]
AID - 10.1093/toxsci/kfi261 [doi]
PST - ppublish
SO  - Toxicol Sci. 2005 Oct;87(2):508-19. doi: 10.1093/toxsci/kfi261. Epub 2005 Jul 27.