Oral exposure to atrazine modulates cell-mediated immune function and decreases host resistance to the B16F10 tumor model in female B6C3F1 mice

Karrow, Niel A.; McCay, J. A.; Brown, R. D.; Musgrove, D. L.; Guo, Tai L.; Germolec, Dori R.; White, Kimber L.

doi:10.1016/j.tox.2004.12.002

Cited by 47 publications

(38 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Animal studies have shown that these tissues are adversely affected by ATR (National Toxicology Program, 1994;Filipov et al, 2005;Karrow et al, 2005;Rodriguez et al, 2005;Pruett et al, 2006;Coban and Filipov, 2007). Our data suggest that ATR is widely distributed and extensively metabolized in mice.…”

Section: Discussionmentioning

confidence: 55%

Disposition of the Herbicide 2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine (Atrazine) and Its Major Metabolites in Mice: A Liquid Chromatography/Mass Spectrometry Analysis of Urine, Plasma, and Tissue Levels

Ross¹,

Jones²,

Filipov³

2008

Drug Metab Dispos

View full text Add to dashboard Cite

2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine (atrazine, ATR)is a toxicologically important and widely used herbicide. Recent studies have shown that it can elicit neurological, immunological, developmental, and biochemical alterations in several model organisms, including in mice. Because disposition data in mice are lacking, we evaluated ATR's metabolism and tissue dosimetry after single oral exposures (5-250 mg/kg) in C57BL/6 mice using liquid chromatography/mass spectrometry (Ross and Filipov, 2006). ATR was metabolized and cleared rapidly; didealkyl ATR (DACT) was the major metabolite detected in urine, plasma, and tissues. Plasma ATR peaked at 1 h postdosing and rapidly declined, whereas DACT peaked at 2 h and slowly declined. Most ATR and metabolite residues were excreted within the first 24 h. However, substantial amounts of DACT were still present in 25-to 48-h and 49-to 72-h urine. ATR reached maximal brain levels (0.06-1.5 M) at 4 h (5-125 mg/kg) and 1 h (250 mg/kg) after dosing, but levels quickly declined to <0.1 M by 12 h in all the groups. In contrast, strikingly high concentrations of DACT (1.5-50 M), which are comparable with liver DACT levels, were detectable in brain at 2 h. Brain DACT levels slowly declined, paralleling the kinetics of plasma DACT. Our findings suggest that in mice ATR is widely distributed and extensively metabolized and that DACT is a major metabolite detected in the brain at high levels and is ultimately excreted in urine. Our study provides a starting point for the establishment of models that link target tissue dose to biological effects caused by ATR and its in vivo metabolites.Atrazine (ATR) is a triazine herbicide that effectively inhibits photosynthesis in broadleaf weeds and grasses (Environmental Protection Agency, 2003). In the United States, ATR is applied on crops such as corn, sugarcane, pineapples, macadamia nuts, and sorghum, as well as on highway and railroad rights-of-way and on evergreen trees (Environmental Protection Agency, 2003). Several epidemiological studies have investigated the link between ATR exposure and adverse human health outcomes (Hoppin et al., 2002;MacLennan et al., 2002;De Roos et al., 2003;Hessel et al., 2004). However, the human data at present are equivocal. In some cases ATR exposure is associated with negative health outcomes, whereas in others it is not. One major drawback of virtually all the existing epidemiological studies is the fact that ATR exposure has not been precisely quantified or estimated. In this regard, exposure-only studies, i.e., studies where health outcomes have not been assessed, indicate that pesticide applicators and farmers during spraying are exposed to appreciable levels of ATR because detectable amounts of ATR and its metabolites are found in their saliva and urine (Hines et al., 2006). Moreover, a recent report indicated that not only ATR applicators but also their families are at risk of high level of ATR exposure (Curwin et al., 2007).Although data on health effects of ATR in humans ar...

show abstract

Section: Discussionmentioning

confidence: 55%

Disposition of the Herbicide 2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine (Atrazine) and Its Major Metabolites in Mice: A Liquid Chromatography/Mass Spectrometry Analysis of Urine, Plasma, and Tissue Levels

Ross¹,

Jones²,

Filipov³

2008

Drug Metab Dispos

View full text Add to dashboard Cite

show abstract

“…A transient reduction in IgM production and T cell reactivity has also been reported after an acute oral exposure (Fournier et al, 1992). Subchronic (2 week) exposure to atrazine decreased resistance to tumor challenge (Karrow et al, 2005). Natural killers were identified as an immune cell targets of atrazine in subchronically exposed mice (Karrow et al, 2005).…”

mentioning

confidence: 83%

“…Subchronic (2 week) exposure to atrazine decreased resistance to tumor challenge (Karrow et al, 2005). Natural killers were identified as an immune cell targets of atrazine in subchronically exposed mice (Karrow et al, 2005). This decrease in natural killer (NK) cell lytic function might explain the observed reduction in tumor resistance.…”

mentioning

confidence: 99%

In vitro atrazine-exposure inhibits human natural killer cell lytic granule release

Rowe

Brundage

Barnett

2007

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

The herbicide atrazine is a known immunotoxicant and an inhibitor of human Natural Killer (NK) cell lytic function. The precise changes in NK cell lytic function following atrazine exposure have not been fully elucidated. The current study identifies the point at which atrazine exerts its affect on the stepwise process of human NK cell mediated lyses of the K562 target cell line. Using intracellular staining of human peripheral blood lymphocytes, it was determined that a 24 h in vitro exposure to atrazine did not decrease the level of NK cell lytic proteins granzyme A, granzyme B or perforin. Thus, it was hypothesized that atrazine exposure was inhibiting the ability of the NK cells to bind to the target cell and subsequently inhibit the release of lytic protein from the NK cell. To test this hypothesis, flow cytometry and fluorescent microscopy were employed to analyze NK cell-target cell co-cultures following atrazine exposure. These assays demonstrated no significant decrease in the level of target cell binding. However, the levels of NK intracellular lytic protein retained and the amount of lytic protein released were assessed following a 4 h incubation with K562 target cells. The relative level of intracellular lytic protein was 25-50% higher, and the amount of lytic protein released was 55-65% less in atrazine treated cells than vehicle treated cells following incubation with the target cells. These results indicate that ATR exposure inhibits the ability of NK cells to lyse target cells by blocking lytic granule release without affecting the ability of the NK cell to form stable conjugates with target cells.

show abstract

“…Exposure to ATR for 14 days can induce a significant decrease in the number of hematopoietic progenitors in murine bone marrow (16), cause a transient suppression of IgM production and T cell proliferation (17), decrease the CD4+ lymphocytes and MHC-II+ cells (18), and increase the mixed lymphocyte reaction (MLR) and cytotoxic T lymphocyte (CTL) response (19). Rajkovic et al reported that ATR increased the number of degranulated mast cells of rats (20).…”

mentioning

confidence: 99%

Sub-acute exposure to the herbicide atrazine suppresses cell immune functions in adolescent mice

et al. 2013

View full text Add to dashboard Cite

Oral exposure to atrazine modulates cell-mediated immune function and decreases host resistance to the B16F10 tumor model in female B6C3F1 mice

Cited by 47 publications

References 27 publications

Disposition of the Herbicide 2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine (Atrazine) and Its Major Metabolites in Mice: A Liquid Chromatography/Mass Spectrometry Analysis of Urine, Plasma, and Tissue Levels

Disposition of the Herbicide 2-Chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine (Atrazine) and Its Major Metabolites in Mice: A Liquid Chromatography/Mass Spectrometry Analysis of Urine, Plasma, and Tissue Levels

In vitro atrazine-exposure inhibits human natural killer cell lytic granule release

Sub-acute exposure to the herbicide atrazine suppresses cell immune functions in adolescent mice

Contact Info

Product

Resources

About