The inhibition of LPS-induced splenocyte proliferation by ortho-substituted and microbially dechlorinated polychlorinated biphenyls is associated with a decreased expression of cyclin D2

Toxicology
L Ashley SmithwickPamela J Morris

Abstract

Immunological effects of polychlorinated biphenyls (PCBs) have been demonstrated in our laboratories with the peferential inhibition of lipopolysaccharide (LPS)-induced splenocyte proliferation by ortho-substituted PCB congeners. An investigation of the mechanism behind this immunotoxicity revealed an interruption in the progression of murine lymphocytes from G0/G1 into S phase by Aroclor 1242 and the di-ortho-substituted congener, 2,2'-chlorobiphenyl (CB), whereas, a non-ortho-substituted congener, 4,4'-CB, did not affect cell cycle progression. This interruption of cell cycle progression by 2,2'-CB and Aroclor 1242 was associated with a decreased expression of the cell cycle regulatory protein, cyclin D2, while expression was not affected by exposure to the non-ortho-substituted 4,4'-CB. These results suggest the preferential inhibition of LPS-induced splenocyte proliferation by ortho-substituted congeners is a result of a decreased expression of cyclin D2, which leads to an interruption in cell cycle progression. In addition, PCB mixtures with an increased percentage of chlorines in the ortho position following an environmentally occurring degradation process inhibited LPS-induced proliferation, interrupted cell cycle progre...Continue Reading

References

Dec 1, 1995·Environmental Health Perspectives·K KrzystyniakM Fournier
Aug 1, 1996·The Journal of Experimental Medicine·N SolvasonM C Howard
Apr 11, 2000·Bulletin of Environmental Contamination and Toxicology·J K WickliffeJ W Bickham
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Feb 13, 2001·Carcinogenesis·B MahadevanW M Baird
Jun 25, 2002·Toxicology and Applied Pharmacology·Bernhard HennigLarry W Robertson

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