Quantitative Analysis of Alachlor Protein Adducts by Gas Chromatography–Mass Spectrometry

Lambert, Guy R.; Padgett, William T.; George, Michael H.; Kitchin, Kirk T.; Nesnow, Stephen

doi:10.1006/abio.1998.3060

Cited by 13 publications

(6 citation statements)

References 17 publications

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“…This species difference appears to result from differences in enterohepatic circulation and tissue specific biotransformation (Hadley and Dahl, 1983; Li et al, 1992), a consequence of which was the greater formation of the reactive diethyliminoquinone biotransformant (Figure 21) in the rat NM. This product binds extensively to glutathione (Jefferies et al, 1998) and thiols in proteins (Lambert et al, 1999), resulting in cytotoxicity and sustained proliferation of the NM (Heydens et al, 1999).…”

Section: Rodent Nasal Carcinogensmentioning

confidence: 99%

Nasal Cytotoxic and Carcinogenic Activities of Systemically Distributed Organic Chemicals

2006

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Toxicity and carcinogenicity in the mucosa of the nasal passages in rodents has been produced by a variety of organic chemicals which are systemically distributed. In this review, 14 such chemicals or classes were identified that produced rodent nasal cytotoxicity, but not carcinogenicity, and 11 were identified that produced nasal carcinogenicity. Most chemicals that affect the nasal mucosa were either concentrated in that tissue or readily activated there, or both. All chemicals with effects in the nasal mucosa that were DNA-reactive, were also carcinogenic, if adequately tested. None of the rodent nasal cytotoxins has been identified as a human systemic nasal toxin. This may reflect the lesser biotransformation activity of human nasal mucosa compared to rodent and the much lower levels of human exposures. None of the rodent carcinogens lacking DNA reactivity has been identified as a nasal carcinogen or other cancer hazard to humans. Some DNA-reactive rodent carcinogens that affect the nasal mucosa, as well as other tissues, have been associated with cancer at various sites in humans, but not the nasal cavity. Thus, findings in only the rodent nasal mucosa do not necessarily predict either a toxic or carcinogenic hazard to that tissue in humans.

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Section: Rodent Nasal Carcinogensmentioning

confidence: 99%

Nasal Cytotoxic and Carcinogenic Activities of Systemically Distributed Organic Chemicals

2006

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“…Hemoglobin is the major hemoproteins of red blood cell (RBC), which can reversibly bind with many kinds of endogenous and exogenous agents such as many drugs (e.g., platinum drugs [14], artemisinins [15], silicotungstic heteropolyacid [16], Fe-porphyrins [17]), herbicides (e.g., Alachlor [18], Aminopielik D [19]), and insecticides (e.g., Chlorpyrifos and Cypermethrin [20]). However, the interaction of PQ with Hb has not been thoroughly investigated.…”

Section: Introductionmentioning

confidence: 99%

Studies of the interaction between paraquat and bovine hemoglobin

Wang

Zhang

et al. 2007

International Journal of Biological Macromolecules

186

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“…Serum-free media is necessary to avoid small molecule scavenging and is a standard incubation condition for cellular exposure to acetochlor 16,50,51 . Indeed, the use of complete media ablates HSR activation by acetochlor.…”

Section: Resultsmentioning

confidence: 99%

Cellular Exposure to Chloroacetanilide Herbicides Induces Distinct Protein Destabilization Profiles

Quanrud

Balamurugan

Canizal

et al. 2022

Preprint

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Herbicides in the popular chloroacetanilide class harbor a potent electrophilic moiety, which can damage proteins through nucleophilic substitution. In general, damaged proteins are subject to misfolding. Accumulation of misfolded proteins compromises cellular integrity by disrupting cellular proteostasis networks, which can further destabilize the cellular proteome. While direct conjugation targets can be discovered through affinity-based protein profiling, there are few approaches to probe how cellular exposure to toxicants impacts the stability of the proteome. We apply a quantitative proteomics methodology to identify chloroacetanilide-destabilized proteins in HEK293T cells based on their binding to the H31Q mutant of the human Hsp40 chaperone DNAJB8. We find that brief cellular exposure to the chloroacetanilides acetochlor, alachlor, and propachlor induces misfolding of dozens of cellular proteins. These herbicides feature distinct but overlapping profiles of protein destabilization, highly concentrated in proteins with reactive cysteine residues. Propachlor induces a general increase in protein aggregation, and selectively targets GAPDH and PARK7, leading to a decrease in their cellular activities. GAPDH is primarily modified by direct conjugation of propachlor at a catalytic cysteine residue, leading to global destabilization of the protein. The Hsp40 affinity strategy is an effective technique to profile cellular proteins that are destabilized by cellular toxin exposure. Raw proteomics data is available through the PRIDE Archive at PXD030635.

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Quantitative Analysis of Alachlor Protein Adducts by Gas Chromatography–Mass Spectrometry

Cited by 13 publications

References 17 publications

Nasal Cytotoxic and Carcinogenic Activities of Systemically Distributed Organic Chemicals

Nasal Cytotoxic and Carcinogenic Activities of Systemically Distributed Organic Chemicals

Studies of the interaction between paraquat and bovine hemoglobin

Cellular Exposure to Chloroacetanilide Herbicides Induces Distinct Protein Destabilization Profiles

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