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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Epigenetic toxicity of hydroxylated biphenyls and hydroxylated polychlorinated biphenyls on normal rat liver epithelial cells.

Authors: Satoh, Andrea Y; Trosko, James E; Masten, Susan J

Published In Environ Sci Technol, (2003 Jun 15)

Abstract: 2-Biphenylol, 3-biphenylol, 2,2'-biphenyldiol, 3,3'-biphenyldiol, 3-chloro-2-biphenylol, and 4,4'-dichloro-3-biphenylol were evaluated using the scrape-loading/dye transfer (SL/ DT) technique to determine in vitro gap junctional intercellular communication (GJIC) in a normal rat liver epithelial cell line as a measure of the epigenetic toxicity. Cytotoxicity was determined using the neutral red uptake assay. A dose range of 0-300 microM was examined. Only 3,3'-biphenyldiol and 4,4'-dichloro-3-biphenylol induced cytotoxicity within the tested dose ranges. Noncytotoxic doses were selected for evaluation of epigenetic toxicity. 4,4'-Dichloro-3-biphenylol was most inhibitory to GJIC at the lowest dose. The cytotoxicity and GJIC inhibitory effects observed for 4,4'-dichloro-3-biphenylol might be, although not exclusively, a consequence of the lipophilic nature of this chemical. 3-Chloro-2-biphenylol was least inhibitory to GJIC. 3-Chloro-2-biphenylol was less inhibitory to GJIC than 2-biphenylol because of the presence of the chlorine functional group, which appears to attenuate the toxic effect of the ortho-hydroxyl group. Although cells were capable of complete recovery of GJIC after removal of each of the chemicals, only with 2,2'-biphenyldiol and 4,4,'-dichloro-3-biphenylol did the cells demonstrate partial recovery without removal of the chemical. The more noncoplanar conformation of 2,2'-biphenyldiol and 2-biphenylol might explain their more inhibitory behavior in comparison to 3,3'-biphenyldiol and 3-biphenylol, respectively.

PubMed ID: 12854712 Exiting the NIEHS site

MeSH Terms: Animals; Biological Assay; Biphenyl Compounds/toxicity*; Cell Survival/drug effects; Cells, Cultured; Environmental Pollutants/toxicity*; Epithelial Cells/cytology; Epithelial Cells/drug effects*; Liver/cytology; Liver/drug effects*; Polychlorinated Biphenyls/toxicity*; Rats; Rats, Inbred F344; Toxicity Tests

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