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Structure‐Function Relationship of PCB‐Mediated Induction of Proinflammatory Mediators In Vivo.
Author(s) -
Sipka Sandor Janos,
Eum Sung Yong,
Pu Hong,
Hennig Bernhard,
Toborek Michal
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a641-a
Subject(s) - proinflammatory cytokine , polychlorinated biphenyl , chemistry , in vivo , biphenyl , stimulation , pharmacology , medicine , toxicology , endocrinology , biology , inflammation , environmental chemistry , microbiology and biotechnology , organic chemistry
Polychlorinated biphenyl (PCB) congeners are a group of worldwide and persistent environmental contaminants. Our research indicated that exposure to specific PCBs can induce vascular alterations, which may result in stimulation of cancer metastasis. Biological properties of PCBs depend on the degree of chlorination and the positions of these substitutions on the biphenyl rings. To establish structure‐function relationship of proinflammatory properties of PCBs, we studied induction of ICAM‐1 and VCAM‐1 in the livers, lungs and brains of mice treated with PCB 77 (a major coplanar PCB), PCB104 (a non‐coplanar PCB with multiple ortho‐chlorine substituents), PCB 118 (a major mono‐ortho substituted PCB) and PCB 153 (a major non‐coplanar PCB) after a single gavaged dose. The strongest expression of proinflammatory proteins occurred 48 h following the PCB administration independent of the class of PCB congeners. In addition, our studies focused to establish the optimum dose of PCBs for induction of these mediators. PCB 77 significantly increased ICAM‐1 mRNA levels in the liver at the dose of 150 μmol/kg and VCAM‐1 protein expression in the liver at the doses of 150 and 200 μmol/kg. Our data suggest that food‐chain exposure to PCBs can induce expression of proinflammatory mediators, which may lead to the development of vascular diseases and cancer metastases. Supported by NIH/NIEHS (P42 ES 07380)