Papers

Peer-reviewed
Mar, 2013

Toxicokinetics of dioxins and other organochlorine compounds in Japanese people: Association with hepatic CYP1A2 expression levels

ENVIRONMENT INTERNATIONAL
  • Michio X. Watanabe
  • ,
  • Tatsuya Kunisue
  • ,
  • Norifumi Ueda
  • ,
  • Masato Nose
  • ,
  • Shinsuke Tanabe
  • ,
  • Hisato Iwata

Volume
53
Number
First page
53
Last page
61
Language
English
Publishing type
Research paper (scientific journal)
DOI
10.1016/j.envint.2012.12.008
Publisher
PERGAMON-ELSEVIER SCIENCE LTD

Concentrations of persistent organochlorine compounds (OCs) including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) in the liver and adipose tissue of Japanese cadavers were measured, and their toxicokinetics were examined in association with hepatic cytochrome P450 (CYP) 1A protein expression levels. Total 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs) were 66 +/- 74 and 65 +/- 57 pg/g lipid weight (mean +/- S.D.) in the liver and adipose tissue, respectively. Total PCBs (sum of 62 congeners targeted), p,p'-dichlorodiphenyl-dichloroethylene (p,p'-DDE) and beta-hexachlorocyclohexane (beta-HCH) were detected at concentrations over 1 mu g/g lipid in both tissues of some specimens. For most of the dioxin-like congeners, total PCBs, p,p'-DDE, oxychlordane, alpha- and beta-HCH, hexachlorobenzene (HCB), and tris(4-chlorophenyl)methane (TCPMe), age-dependent increases in concentrations were found in the adipose tissue of males. No such age-dependent trend was observed in the liver, suggesting that there are different mechanisms underlying the hepatic concentrations of OCs. Immunoblot analyses indicated detectable expression of hepatic CYP1A2 protein, whereas no CYP1A1 protein was detected. The CYP1A2 expression levels were positively correlated with concentrations (on wet weight basis) of 2,3,4,7,8-P5CDF, the dominant TEQ-contributed congeners in the liver, indicating the induction of this CYP. Hepatic CYP1A2 protein levels were strongly correlated with the liver to adipose concentration (L/A) ratios of PCDD/F congeners with more than 5 chlorine atoms. Together with higher concentrations of the congeners in the liver than in the adipose tissue, the observation on L/A ratios of highly chlorinated PCDD/Fs suggests that induced hepatic CYP1A2 protein is involved in their sequestration in this human population, as observed in model animals (rodents). Nonetheless, the magnitude of hepatic sequestration (L/A ratio) of PCDD/Fs in this human population was lower than in other mammals and birds, reported previously. This study emphasizes the fact that toxicokinetics of some OCs can be affected at least partly by CYP1A2 protein levels in humans. For the extrapolation of their toxicokinetics from model animals to humans, knowledge on the induction and sequestration potencies of CYP1A is necessary. (C) 2013 Elsevier Ltd. All rights reserved.

Link information
DOI
https://doi.org/10.1016/j.envint.2012.12.008
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/23333656
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000315551700007&DestApp=WOS_CPL
ID information
  • DOI : 10.1016/j.envint.2012.12.008
  • ISSN : 0160-4120
  • Pubmed ID : 23333656
  • Web of Science ID : WOS:000315551700007

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