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2L (1) - Immunotoxicity - genotoxicity - ED (WE8/7) Cytotoxic, mitogenic and estrogenic effects of pentachlorophenol in primary hepatocyte cultures obtained from channel catfish (Ictalarus punctatus). Tchounwou, Paul1, Dorsey, Waneene1, 1 Molecular Toxicology Research Laboratory, Jackson State University, Jackson, Mississippi, USA ABSTRACT- Cytotoxic, mitogenic and estrogenic effects of pentachlorophenol in primary hepatocyte cultures obtained from channel catfish (Ictalarus punctatus). Tchounwou P.B. and Dorsey W.C. Molecular Toxicology Research Laboratory, Jackson State University, Jackson, Mississippi, USA. Pentachlorophenol (PCP) is an organochloride 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 cytotoxicty and transcriptionally activates stress genes in human liver carcinoma (HepG2) cells (Dorsey et al., Int. J. Mol. Sci., 3:1002-1007, 2002). 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 ug/mL. The NOAEL and LOAEL were 62.5+10.3 ug/mL and 125.0+15.2 ug/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 upregulation of the 125-kDa vitellogenin protein in the hepatocytes of male channel catfish. [Research supported by the National Institutes of Health (Grant N0.1G12RR13459), through the NCRR-RCMI Center for Environmental Health at Jackson State University]. Key words: cytotoxicity, pentachlorophenol, estrogenicity, catfish |
