3-Aminobenzamide: Effects on Cytochrome P450-Dependent Metabolism of Chemicals and on the Toxicity of Dichlobenil in the Olfactory Mucosa

Eriksson, Catarina; Busk, Leif; Brittebo, Eva B.

doi:10.1006/taap.1996.0039

Cited by 13 publications

(7 citation statements)

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“…Olfactory toxicity is often related to a tissue-specific and cytochrome P450 (CYP) -dependent metabolic activation of the chemicals into reactive intermediates (Eriksson and Brittebo 1991;Brittebo et al 1992;Brittebo 1995;Ding et al 1996;Eriksson et al 1996;Bergman and Brittebo 1999). The olfactory toxicants dichlobenil (a herbicide) and methimazole (a drug used in hyperthyroidism) were selected for this study.…”

Section: Introductionmentioning

confidence: 99%

Differential effects of olfactory toxicants on olfactory regeneration

Bergman

Östergren²,

Gustafson

et al. 2002

Archives of Toxicology

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The aim was to study the long-term response in the olfactory mucosa of NMRI mice after exposure to the olfactory toxicants dichlobenil (a herbicide) or methimazole (an antithyroid drug). Three and six months after exposure to dichlobenil (2x or 1 x 25 mg/kg i.p.), the dorsomedial part of the olfactory region showed a respiratory metaplasia with abundant invaginations and a fibrotic lamina propria. In contrast, 3 months after exposure to a toxic dose of methimazole (2 x 50 mg/kg i.p.), the olfactory neuroepithelium and lamina propria had been restored. To study the regenerative events, we used an antibody derived against growth-associated protein 43 (GAP-43), which stains immature neurons. To study epithelial differentiation and horizontal basal cells (HBCs) we used an antibody derived against some cytokeratins. Two weeks after methimazole treatment, there was a marked increase of GAP-43-stained cells in the whole olfactory region, which correlated with the observed regeneration at that time. Two weeks after dichlobenil treatment, the damaged atypical epithelium in the olfactory region showed a distinct keratin staining of basal and columnar cells whereas GAP-43-stained cells were not found. Despite a transient increase of GAP-43-stained cells in the border zone between damaged and undamaged olfactory mucosa, an expansion of a normal neuroepithelium into the damaged olfactory region was not detected in the dichlobenil-treated mice. An intact lamina propria is suggested as a prerequisite for repopulation of the neuroepithelium after toxicant-induced injury.

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Section: Introductionmentioning

confidence: 99%

Differential effects of olfactory toxicants on olfactory regeneration

Bergman

Östergren²,

Gustafson

et al. 2002

Archives of Toxicology

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“…As a PARP inhibitor, 3AB lacks potency and specificity (Milam et al, 1986;Eriksson et al, 1996). It has been shown that potentiation of the activity of cytotoxic drugs by 3AB can be via PARPindependent mechanisms (Moses et al, 1988a;1988b;.…”

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confidence: 99%

Differential effects of the poly (ADP-ribose) polymerase (PARP) inhibitor NU1025 on topoisomerase I and II inhibitor cytotoxicity in L1210 cells in vitro

et al. 2001

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The potent novel poly(ADP-ribose) polymerase (PARP) inhibitor, NU1025, enhances the cytotoxicity of DNA-methylating agents and ionizing radiation by inhibiting DNA repair. We report here an investigation of the role of PARP in the cellular responses to inhibitors of topoisomerase I and II using NU1025. The cytotoxicity of the topoisomerase I inhibitor, camptothecin, was increased 2.6-fold in L1210 cells by co-incubation with NU1025. Camptothecin-induced DNA strand breaks were also increased 2.5-fold by NU1025 and exposure to camptothecin-activated PARP. In contrast, NU1025 did not increase the DNA strand breakage or cytotoxicity caused by the topoisomerase II inhibitor etoposide. Exposure to etoposide did not activate PARP even at concentrations that caused significant levels of apoptosis. Taken together, these data suggest that potentiation of camptothecin cytotoxicity by NU1025 is a direct result of increased DNA strand breakage, and that activation of PARP by camptothecin-induced DNA damage contributes to its repair and consequently cell survival. However, in L1210 cells at least, it would appear that PARP is not involved in the cellular response to etoposide-mediated DNA damage. On the basis of these data, PARP inhibitors may be potentially useful in combination with topoisomerase I inhibitor anticancer chemotherapy. © 2001 Cancer Research Campaign http://www.bjcancer.com

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“…For instance, 3AB protects primary human keratinocytes from UV-induced cell death, but this phenotype was not reproduced with the inhibitor PJ-34 or with silencing of PARP1, indicating a poly(ADP-ribosyl)ation independent mechanism (Lakatos et al, 2013). In other studies 3AB has been shown to inhibit protein kinase C (Ricciarelli et al, 1998), certain cytochrome P450s (Eriksson et al, 1996), and to act as a hydroxyl radical scavenger (Czapski et al, 2004). Our study adds to the list of processes separate from poly(ADP-ribosyl)ation that are targeted by 3AB, demonstrating inhibition of MAMP-induced callose deposition as a new off-target effect of 3AB in plants.…”

Section: Discussionmentioning

confidence: 94%

3-Aminobenzamide Blocks MAMP-Induced Callose Deposition Independently of Its Poly(ADPribosyl)ation Inhibiting Activity

et al. 2018

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Cell wall reinforcement with callose is a frequent plant response to infection. Poly(ADP-ribosyl)ation is a protein post-translational modification mediated by poly(ADP-ribose) polymerases (PARPs). Poly(ADP-ribosyl)ation has well-known roles in DNA damage repair and has more recently been shown to contribute to plant immune responses. 3-aminobenzamide (3AB) is an established PARP inhibitor and it blocks the callose deposition elicited by flg22 or elf18, two microbe-associated molecular patterns (MAMPs). However, we report that an Arabidopsis parp1parp2parp3 triple mutant does not exhibit loss of flg22-induced callose deposition. Additionally, the more specific PARP inhibitors PJ-34 and INH2BP inhibit PARP activity in Arabidopsis but do not block MAMP-induced callose deposition. These data demonstrate off-target activity of 3AB and indicate that 3AB inhibits callose deposition through a mechanism other than poly(ADP-ribosyl)ation. POWDERY MILDEW RESISTANT 4 (PMR4) is the callose synthase responsible for the majority of MAMP- and wound-induced callose deposition in Arabidopsis. 3AB does not block wound-induced callose deposition, and 3AB does not reduce the PMR4 mRNA abundance increase in response to flg22. Levels of PMR4-HA protein increase in response to flg22, and increase even more in flg22 + 3AB despite no callose being produced. The callose synthase inhibitor 2-deoxy-D-glucose does not cause similar impacts on PMR4-HA protein levels. Beyond MAMPs, we find that 3AB also reduces callose deposition induced by powdery mildew (Golovinomyces cichoracearum) and impairs the penetration resistance of a PMR4 overexpression line. 3AB thus reveals pathogenesis-associated pathways that activate callose synthase enzymatic activity distinct from those that elevate PMR4 mRNA and protein abundance.

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3-Aminobenzamide: Effects on Cytochrome P450-Dependent Metabolism of Chemicals and on the Toxicity of Dichlobenil in the Olfactory Mucosa

Cited by 13 publications

References 0 publications

Differential effects of olfactory toxicants on olfactory regeneration

Differential effects of olfactory toxicants on olfactory regeneration

Differential effects of the poly (ADP-ribose) polymerase (PARP) inhibitor NU1025 on topoisomerase I and II inhibitor cytotoxicity in L1210 cells in vitro

3-Aminobenzamide Blocks MAMP-Induced Callose Deposition Independently of Its Poly(ADPribosyl)ation Inhibiting Activity

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