Pentachlorophenol decreases ATP levels in human natural killer cells

Abstract

Pentachlorophenol (PCP) is used as a wood preservative and is found in human blood and urine. PCP causes significant decreases in the tumor-killing (lytic) function of human natural killer (NK) cells, a critical immune defense. The current study examined the association between decreased lytic function and decreased ATP levels, as well as the ability of antioxidants (vitamin E and reduced glutathione) to prevent PCP-induced decreases in either ATP levels or lytic function. Exposure of NK cells to 10μM PCP decreased ATP levels by 15% at 24 h, and exposure to 5 μM PCP decreased ATP levels by 32% at 48 h. No effects were seen with 0.5 μM at 48 h or with 5 μM at 24 h. However, 10 μM PCP decreased lytic function by 69% at 24h and 5 μM decreased it by 90% at 48 h. Even 0.5 μM PCP decreased lytic function by 46% at 48 h. None of these effects were prevented by pretreatment with 1 mM vitamin E or reduced glutathione.

Effects of pentachlorophenol and dichlorodiphenyltrichloroethane on secretion of interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) from human immune cells

“…Both DDT and PCP are associated with increases in the incidences of certain cancers (Demers et al, 2006; Cohn et al, 2007). Past studies have shown that both PCP and DDT inhibit the lytic function of human NK cells and decrease their expression of key cell surface proteins (Udoji et al, 2010; Reed et al, 2004; Taylor et al, 2005; Nnodu & Whalen, 2008; Hurd et al, 2013). …”

“…Previous studies have shown that exposure to PCP for 24 h lead to decreases in the ability of NK lymphocytes to destroy tumor cells (lytic function) (Reed et al, 2004, Nnodu & Whalen, 2008). Decreases in lytic function were seen at higher PCP concentrations while concentrations below 0.5 μM had no effect on this function.…”

“…Additionally, both of these compounds decreased the ability of NK cells to bind to tumor target cells (Reed et al, 2004; Nnodu & Whalen, 2008; Udoji et al, 2010; Hurd et al, 2012; Hurd-Brown et al, 2013) while decreasing the expression of certain cell-surface proteins needed for the binding process (Hurd et al, 2012; Hurd-Brown et al, 2013). Based on the results from previous studies on the effects of PCP and DDT on immune function we hypothesize that PCP and DDT may alter the secretion of IFNγ and/or TNFα from human immune cells.…”

Exposures to the environmental toxicants pentachlorophenol (PCP) and dichlorodiphenyltrichloroethane (DDT) modify secretion of interleukin 1-beta (IL-1β) from human immune cells

“…PCP exposure has been associated with kidney cancer, lymphoma, and myeloma (Demers et al, 2006) while DDT exposure is linked to increased incidences of liver, pancreatic, breast, and testicular cancers as well as leukemia (Eskanazi et al, 2009; Cohn et al, 2007; Snedeker & Stapleton, 2009). Studies have shown that the tumor binding (Hurd et al, 2012; Hurd-Brown et al, 2013) and lysing function (Reed et al, 2004; Nnodu and Whalen, 2008) of human NK lymphocytes as well as their expression of important cell surface proteins (Hurd et al, 2012; Hurd-Brown et al, 2013) is decreased by ex vivo exposure to PCP and DDT. IL-1β in its role as a pro-inflammatory cytokine is a master regulator of the immune response (Sahoo et.…”

“…Results of prior ex vivo studies indicate that exposure of human NK cells to both PCP and DDT causes inhibition of their ability to bind and lyse tumor target cells (Reed et al, 2004; Nnodu and Whalen, 2008; Udoji et al, 2010; Hurd et al, 2012; Hurd-Brown et al, 2013). Both compounds also decrease the expression of certain cell-surface proteins needed for NK lymphocytes to bind to tumor targets (Hurd et al, 2012; Hurd-Brown et al, 2013).…”