التفاصيل البيبلوغرافية
| العنوان: |
Activation of the human TRPA1 channel by different alkylating sulfur and nitrogen mustards and structurally related chemotherapeutic drugs. |
| المؤلفون: |
Müller-Dott, Katharina1,2 (AUTHOR) k.muellerdott@campus.lmu.de, Raßmuß, Sarah Christine1 (AUTHOR) s.rassmuss@labor-becker.de, Blum, Marc-Michael1 (AUTHOR) mmblum@blum-scientific.de, Thiermann, Horst1 (AUTHOR) horstthiermann@bundeswehr.org, John, Harald1 (AUTHOR) haraldjohn@bundeswehr.org, Steinritz, Dirk1,2 (AUTHOR) dirksteinritz@bundeswehr.org |
| المصدر: |
Toxicology Letters. Mar2023, Vol. 376, p51-59. 9p. |
| مصطلحات موضوعية: |
*MUSTARD gas, *NITROGEN mustards, *CHEMICAL warfare agents, *CONOTOXINS, *ALKYLATING agents, *CANCER chemotherapy, *CALCIUM ions |
| مستخلص: |
An important target in toxicology is the ion channel known as human transient receptor potential ankyrin 1 (hTRPA1). It is triggered by a variety of chemicals, including the alkylating chemical warfare agent sulfur mustard (SM). The activation potentials of structural analogs including O- and sesquimustard, nitrogen mustards (HN1, HN2, and HN3), and related chemotherapeutic drugs (bendamustine, cycylophosphamide, and ifosfamide) were examined in the current study. The aequorin assay was used to measure changes in intracellular calcium levels in human hTRPA1 overexpressing HEK293 cells. The XTT assay was used to determine cytotoxicity. The data presented here highlight that all investigated alkylating substances, with the exception of cyclophosphamide and ifosfamide, cause the activation of hTRPA1. Cytotoxicity and activation of hTRPA1 were found to be related. Compounds with high reactivity had higher cytotoxicity and vice versa. However, inhibiting hTRPA1 with the specific inhibitor AP18 could not reduce the cytotoxicity induced by alkylating agents. As a result, hTRPA1 does not play a significant role in the cytotoxicity of alkylating agents. • hTRPA1 is activated by SM-related alkylating compounds. • Cytotoxicity and hTRPA1 activation were shown to be related. • Substances that prominently activate hTRPA1 were shown to be more cytotoxic. • hTRPA1 inhibition does not generally reduce cytotoxicity. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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