title: Pentachlorophenol-induced cytotoxic, mitogenic, and endocrine-disrupting activities in channel catfish, Ictalurus punctatus.
abstract: Pentachlorophenol (PCP) is an organochlorine compound that has been widely used as a biocide in several industrial, agricultural, and domestic applications. Although it has been shown to induce systemic toxicity and carcinogenesis in several experimental studies, the literature is scarce regarding its toxic mechanisms of action at the cellular and molecular levels. Recent investigations in our laboratory have shown that PCP induces cytotoxicity and transcriptionally activates stress genes in human liver carcinoma (HepG2) cells [1]. In this research, we hypothesize that environmental exposure to PCP may trigger cytotoxic, mitogenic, and endocrine-disrupting activities in aquatic organisms including fish. To test this hypothesis, we carried out in vitro cultures of male channel catfish hepatocytes, and performed the fluorescein diacetate assay (FDA) to assess for cell viability, and the Western Blot analysis to assess for vitellogenin expression following exposure to PCP. Data obtained from FDA experiments indicated a strong dose-response relationship with respect to PCP cytotoxicity. Upon 48 hrs of exposure, the chemical dose required to cause 50% reduction in cell viability (LD50) was computed to be 1,987.0 +/- 9.6 microg PCP/mL. The NOAEL and LOAEL were 62.5 +/- 10.3 microg PCP/mL and 125.0+/-15.2 microg PCP/mL, respectively. At lower levels of exposure, PCP was found to be mitogenic, showing a strong dose- and time-dependent response with regard to cell proliferation. Western Blot analysis demonstrated the potential of PCP to cause endocrine-disrupting activity, as evidenced by the up regulation of the 125-kDa vitellogenin protein the hepatocytes of male channel catfish.
authors.affiliation: Molecular Toxicology Research Laboratory, NIH - Center for Environmental Health, School of Science and Technology, Jackson State University, 1400 Lynch Street, P.O. Box 18540, Jackson, Mississippi, USA.
authors.forename: Waneene C
authors.initials: WC
authors.lastname: Dorsey
authors.forename: Paul B
authors.initials: PB
authors.lastname: Tchounwou
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D007059:Ictaluridae / Q000378:metabolism*; D008297:Male; D008934:Mitogens / Q000633:toxicity*; D010416:Pentachlorophenol / Q000633:toxicity*; D010575:Pesticides / Q000633:toxicity; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D014819:Vitellogenins / Q000235:genetics / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity
chemical_list: D004785:Environmental Pollutants; D008934:Mitogens; D010575:Pesticides; D016760:Proto-Oncogene Proteins c-fos; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; D010416:Pentachlorophenol