In vitro oxidation of alachlor by liver microsomal enzymes from rats, mice, and monkeys

Feng, Pengfei; Patanella, J E

doi:10.1016/0048-3575(89)90072-2

Cited by 23 publications

(13 citation statements)

References 9 publications

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“…Therefore, it seems likely that intermediate metabolites of alachlor are formed initially in an extranasal tissue and subsequently transported to the olfactory mucosa. Further support for this possibility rests in the observation that 2,6-diethylaniline, which is believed to be a pivotal metabolite of alachlor (11), can be detected in the blood following IP injection of alachlor (14). Therefore, the present data provide substantial support for delivery of an intermediate alachlor metabolite to the nasal mucosa via the bloodstream, with subsequent bioactivation in the nasal mucosa.…”

Section: Methodsmentioning

confidence: 99%

Evolution of Alachlor-Induced Nasal Neoplasms in the Long-Evans Rat

et al. 2000

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Section: Methodsmentioning

confidence: 99%

Evolution of Alachlor-Induced Nasal Neoplasms in the Long-Evans Rat

et al. 2000

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“…Liver Microsomal Incubations. Microsomal incubations (1-3 mg of protein) were conducted in open reaction vials containing an NADPH-generating system (Feng and Patanella, 1989), pH 7.4 phosphate buffer (0.2 M), and labeled triallate substrate (0.05 Mmol) in a total volume of 1 mL containing 5% methanol. Incubations were stirred at 37 6 C in a water bath.…”

Section: Chemicalsmentioning

confidence: 99%

“…Reactions were initiated by addition of substrate and were quenched at intervals of 2,10,35,65, and 120 min with an equal volume of cold methanol. Since both triallate and TCPSA were unreactive under these conditions, the activity of the liver cytosolic preparation was confirmed by incubating with alachlor, which reacts rapidly with GSH when incubated with rat liver cytosol (Feng and Patanella, 1989).…”

Section: Chemicalsmentioning

confidence: 99%

Metabolism of triallate in Sprague-Dawley rats. 3. In vitro metabolic pathways

Hackett¹,

Kotyk²,

Fujiwara³

et al. 1993

J. Agric. Food Chem.

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Rat liver enzyme preparations were used to investigate the mechanistic pathways of triallate metabolism. Incubation of [14C]triallate with NADPH-fortified microsomes gave rise to metabolites generated via a number of reaction types, including sulfur oxidation/hydrolysis and hydroxylation of the allylic thiol moiety accompanied by rearrangement. Addition of glutathione (GSH) to microsomal incubations resulted in the formation of GSH conjugates arising via conjugate addition of glutathione to metabolic intermediates such as trichloroacrolein. Addition of GSH to microsomal incubations inhibited the binding of triallate-derived radioactivity to microsomal proteins. Metabolite identification was accomplished by mass spectrometry and chemical synthesis and by a novel application of heteronuclear multiple quantum coherence (HMQC) NMR spectroscopy. Elucidation of the in vitro metabolism of triallate provides important mechanistic information regarding triallate metabolism in the laboratory rat.

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“…[1][2][3] Although the mechanism for carcinogenicity of alachlor has not been elucidated, it has been proposed that alachlor forms a DNA reactive metabolite, 3,5-diethylbenzoquinone 4-imine. [4][5][6] Feng and Patanella 7,8 have reported in vitro studies with liver homogenates which identified two major pathways of alachlor metabolism in rats, mice and monkeys. They demonstrated that alachlor is converted to a glutathione conjugate by cytosolic glutathione and oxidative products by the microsomal cytochrome P450 system.…”

Section: Introductionmentioning

confidence: 99%

Effect of Alachlor on Hepatic Cytochrome P450 Enzymes in Rats

Hanioka

Watanabe²,

Yoda³

et al. 2002

Drug and Chemical Toxicology

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Alachlor ((2-chloro-N-methoxymethyl)-N-(2,6-diethylphenyl)acetamide) is a widely used preemergence herbicide which has been classified by the USEPA as a probable human carcinogen. The herbicide has been suggested to be metabolized by hepatic cytochrome P450 system. We examined the effects of alachlor on cytochrome P450 enzymes in rat liver microsomes. Rats were treated intraperitoneally with alachlor daily for 5 days, at doses of 25, 50 and 100 mg/kg. Among the cytochrome P450-dependent monooxygenase activities, 7-pentoxyresorufin O-depentylase, which is associated with CYP2B1, was dose-dependently increased by alachlor. The induction relative to control activity was 1.7-4.2-fold. The activities of CYP1A-dependent monooxygenases such as 7-ethoxy-resorufin O-deethylase and acetanilide 4-hydroxylase were also significantly increased by alachlor at doses of 50 and 100 mg/kg (1.7-2.1-fold). Furthermore, immunoblotting showed that alachlor significantly increased CYP2B1/2 and CYP1A1/2 protein levels by 4.2-6.3- and 1.8-fold, respectively. Although 7-ethoxycoumarin O-deethylase, bufuralol 1'-hydroxylase and 4-nitrophenol 2-hydroxylase activities were significantly increased by alachlor at higher doses (> or = 50 mg/kg), the induction ratios were less than 1.6-fold. The activities of other cytochrome P450-dependent monooxygenases, namely testosterone 7 alpha-hydroxylase, testosterone 2 alpha-hydroxylase, testosterone 6 beta-hydroxylase and lauric acid omega-hydroxylase, were not affected by alachlor at any dose. In addition, there was no significant change in the protein levels of CYP2C11/6, CYP2D1, CYP2E1, CYP3A2/1 and CYP4A1/2/3. These results suggest that alachlor selectively induces cytochrome P450 isoforms of the CYP1A and CYP2B subfamilies in rat liver microsomes, and that the expression of these isoforms is closely related to the toxicity of alachlor.

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In vitro oxidation of alachlor by liver microsomal enzymes from rats, mice, and monkeys

Cited by 23 publications

References 9 publications

Evolution of Alachlor-Induced Nasal Neoplasms in the Long-Evans Rat

Evolution of Alachlor-Induced Nasal Neoplasms in the Long-Evans Rat

Metabolism of triallate in Sprague-Dawley rats. 3. In vitro metabolic pathways

Effect of Alachlor on Hepatic Cytochrome P450 Enzymes in Rats

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