Epigenetic toxicity of hydroxylated biphenyls and hydroxylated polychlorinated biphenyls on normal rat liver epithelial cells.
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.
Satoh
Andrea Y
AY
Department of Civil and Environmental Engineering, Michigan State University, East Lansing, Michigan 48824, USA.
Trosko
James E
JE
Masten
Susan J
SJ
D000818:Animals; D001681:Biological Assay; D001713:Biphenyl Compounds / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004785:Environmental Pollutants / Q000633:toxicity*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D018675:Toxicity Tests
D001713:Biphenyl Compounds; D004785:Environmental Pollutants; D011078:Polychlorinated Biphenyls