Mitogenic and cytotoxic effects of pentachlorophenol to AML 12 mouse hepatocytes.
Pentachlorophenol (PCP), an organochlorine fungicide, is extensively used in the United States for the protection of wood products. Moreover, widespread agricultural, domestic, and industrial applications have caused PCP-contaminants to enter the food chain from the environment. There is accumulating evidence indicating that PCP is highly toxic to humans, and causes injury to major organs including the lung, liver, kidneys, heart, and brain. While PCP has been shown to induce systemic toxicity and carcinogenesis in several experimental studies, the literature is scarce regarding its toxic mechanisms of action. Recent investigations in our laboratory have shown that PCP exerts both cytotoxic and mitogenic effects in human liver carcinoma (HepG2) cells [1], and in primary culture of catfish hepatocytes [2]. In the present study, we hypothesized that PCP exposure will trigger similar cytotoxic and mitogenic responses in AML 12 Mouse hepatocytes. To test this hypothesis, we performed the MTT assay for cell viability in PCP-treated and control cells. Data obtained from this experiment indicated a biphasic response with respect to PCP toxicity; showing a hormosis effect characterized by mitogenicity at lower levels of exposure, and cytotoxicity at higher doses. Upon 48 hrs of exposure, PCP chemical doses required to cause 50% reduction in the viability (LC50) of AML 12 mouse hepatocytes was computed to be 16.0 + 2.0 microg/mL. These results indicate that, although the sensitivity to PCP toxicity varies from one cell line to another, its toxic mechanisms are similar across cell lines.
Dorsey
Waneene C
WC
Wildlife Biology Unit, Grambling State University, Grambling, LA 71245, USA. dorseywc2002@yahoo.com
Tchounwou
Paul B
PB
Sutton
Dwayne
D
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008934:Mitogens / Q000633:toxicity*; D010416:Pentachlorophenol / Q000633:toxicity*; D010575:Pesticides / Q000633:toxicity*
D008934:Mitogens; D010575:Pesticides; D010416:Pentachlorophenol