Immunomodulatory effects of maternal atrazine exposure on male Balb/c mice

Rowe, Alexander M.; Brundage, Kathleen M.; Schafer, Rosana; Barnett, John B.

doi:10.1016/j.taap.2005.12.006

Cited by 51 publications

(53 citation statements)

References 38 publications

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“…Rowe et al used timerelease pellets to subcutaneously expose pregnant Balb/c dams to 700 μg/day of ATR for 21 days from day 10 and day 12 of pregnancy. At 3 months of age, male, but not female, mouse pups had increases in T cell proliferation, cytolytic activity, and the number of IgM-secreting B cells in the spleen, but there were no marked changes in the body weight, organ-to-body weight ratio of the spleen, and the numbers of CD8+ T cells, CD4+ T cells, and B220+ B cells in the spleen (25).…”

mentioning

confidence: 87%

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

et al. 2013

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mentioning

confidence: 87%

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

et al. 2013

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“…Besides effects on the nervous system, ATR exposure can adversely affect the immune system, with thymus being affected more than the spleen shortly after exposure (National Toxicology Program, 1994;Pruett et al, 2003;Filipov et al, 2005;Karrow et al, 2005;Rowe et al, 2006). However, thymus cellularity seems to recover from the effects of ATR, whereas splenic cellularity is reduced up to 7 weeks after exposure termination (Filipov et al, 2005).…”

Section: Ross Et Almentioning

confidence: 99%

“…Although data on health effects of ATR in humans are not complete, an increasing number of animal studies report that ATR exposure causes reproductive, developmental, and immunological alterations in laboratory rodents (Cooper et al, 1996Narotsky et al, 2001;Pruett et al, 2003;Filipov et al, 2005;Giusi et al, 2006;Rowe et al, 2006). The brain is another potential target organ for ATR as several in vitro and in vivo studies have suggested that excessive exposure to ATR may be neurotoxic (Das et al, 2000(Das et al, , 2001Rodriguez et al, 2005;Giusi et al, 2006;Coban and Filipov, 2007).…”

mentioning

confidence: 99%

“…Most of the above-mentioned studies have been performed in rats (Cooper et al, 1996Narotsky et al, 2001;Rodriguez et al, 2005). However, mice are increasingly used in toxicology research, and the number of studies using mice for the assessment of potential adverse consequences of ATR exposure is increasing (National Toxicology Program, 1994;Pruett et al, 2003;Filipov et al, 2005;Giusi et al, 2006;Rowe et al, 2006;Coban and Filipov, 2007).…”

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confidence: 99%

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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

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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...

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“…1 Adverse effects of atrazine also affect human health. 2 In fact, atrazine is an endocrine disruptor and corelates with breast and reproductive disorders in mammalians. 3 Atrazine at present is widely used in USA and, although it has been withdrawn from the market in several European countries, analogous molecules (as terbuthylazine differing only by side chain methyl groups) are currently used.…”

Section: Introductionmentioning

confidence: 99%

Structure‐based design of novel Chlamydomonas reinhardtii D1‐D2 photosynthetic proteins for herbicide monitoring

et al. 2009

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The D1-D2 heterodimer in the reaction center core of phototrophs binds the redox plastoquinone cofactors, Q A and Q B , the terminal acceptors of the photosynthetic electron transfer chain in the photosystem II (PSII). This complex is the target of the herbicide atrazine, an environmental pollutant competitive inhibitor of Q B binding, and consequently it represents an excellent biomediator to develop biosensors for pollutant monitoring in ecosystems. In this context, we have undertaken a study of the Chlamydomonas reinhardtii D1-D2 proteins aimed at designing site directed mutants with increased affinity for atrazine. The three-dimensional structure of the D1 and D2 proteins from C. reinhardtii has been homology modeled using the crystal structure of the highly homologous Thermosynechococcus elongatus proteins as templates. Mutants of D1 and D2 were then generated in silico and the atrazine binding affinity of the mutant proteins has been calculated to predict mutations able to increase PSII affinity for atrazine. The computational approach has been validated through comparison with available experimental data and production and characterization of one of the predicted mutants. The latter analyses indicated an increase of one order of magnitude of the mutant sensitivity and affinity for atrazine as compared to the control strain. Finally, D1-D2 heterodimer mutants were designed and selected which, according to our model, increase atrazine binding affinity by up to 20 kcal/mol, representing useful starting points for the development of high affinity biosensors for atrazine.

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Immunomodulatory effects of maternal atrazine exposure on male Balb/c mice

Cited by 51 publications

References 38 publications

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

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

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

Structure‐based design of novel Chlamydomonas reinhardtii D1‐D2 photosynthetic proteins for herbicide monitoring

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