Epigenetic Toxicity of Hydroxylated Biphenyls and Hydroxylated Polychlorinated Biphenyls on Normal Rat Liver Epithelial Cells

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.

Effects of Polychlorinated Biphenyls 28, 30 and 118 on Bovine Spermatozoa In Vitro

“…); act as tumour promoter by alternating/inhibiting gap junctional intercellular communication (Satoh et al. ) which was referred for its important role for male reprotoxicity (Cai et al. ), induce genotoxicity or interact with aryl hydrocarbon receptor (AHR) (Meeker and Hauser ).…”

Effect of byproducts from the ozonation of pyrene: Biphenyl‐2,2′,6,6′‐tetracarbaldehyde and biphenyl‐2,2′,6,6′‐tetracarboxylic acid on gap junction intercellular communication and neutrophil function

“…Cells were cultured using the method described in detail by Luster-Teasley et al [22] and Satoh et al [42]. Tsao of the University of North Carolina (Chapel Hill, NC, USA).…”

“…Tsao of the University of North Carolina (Chapel Hill, NC, USA). The area of fluorescent cells was measured using a Gel Expert Program by NucleoTech [21], Luster-Teasley et al [22], and Satoh et al [42]. Bioassay for GJIC.…”

“…Tsao of the University of North Carolina (Chapel Hill, NC, USA). Cells were cultured using the method described in detail by Luster-Teasley et al [22] and Satoh et al [42]. Bioassay for GJIC.…”

“…Gap junctional intercellular communication was assessed by the decrease in communication of the cells exposed to the toxicant compared to the vehicle control group (ACN only). [22], and Satoh et al [42]. Controls were run for each experiment to standardize the measurement for normal cell-cell communication at the time of the experiment.…”