New aminobiphenylcysteine derivatives in globin and urine of rats dosed with 4-aminobiphenyl, a tobacco smoke carcinogen

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F75010330%3A_____%2F23%3A00014189" target="_blank" >RIV/75010330:_____/23:00014189 - isvavai.cz</a>

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acs.chemrestox.2c00366" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.chemrestox.2c00366</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.chemrestox.2c00366" target="_blank" >10.1021/acs.chemrestox.2c00366</a>

Jazyk výsledku

angličtina

Název v původním jazyce

New aminobiphenylcysteine derivatives in globin and urine of rats dosed with 4-aminobiphenyl, a tobacco smoke carcinogen

Popis výsledku v původním jazyce

The 4-biphenylnitrenium ion (BPN), a reactive metabolic intermediate of the tobacco smoke carcinogen 4-aminobiphenyl (4-ABP), can react with nucleophilic sulfanyl groups in glutathione (GSH) as well as in proteins. The main site of attack of these S-nucleophiles was predicted using simple orientational rules of aromatic nucleophilic substitution. Thereafter, a series of presumptive 4-ABP metabolites and adducts with cysteine were synthesized, namely, S-(4-amino-3-biphenyl)cysteine (ABPC), N-acetyl-S-(4-amino-3-biphenyl)cysteine (4-amino-3-biphenylmercapturic acid, ABPMA), S-(4-acetamido-3-biphenyl)cysteine (AcABPC), and N-acetyl-S-(4-acetami-do-3-biphenyl)cysteine (4-acetamido-3-biphenylmercapturic acid, AcABP-MA). Then, globin and urine of rats dosed with a single ip dose of 4-ABP (27 mg/kg b.w.) was analyzed by HPLC-ESI-MS2. ABPC was identified in acid-hydrolyzed globin at levels of 3.52 +/- 0.50, 2.74 +/- 0.51, and 1.25 +/- 0.12 nmol/g globin (mean +/- S.D.; n = 6) on days 1, 3, and 8 after dosing, respectively. In the urine collected on day 1 (0-24 h) after dosing, excretion of ABPMA, AcABPMA, and AcABPC amounted to 1.97 +/- 0.88, 3.09 +/- 0.75, and 3.69 +/- 1.49 nmol/kg b.w. (mean +/- S.D.; n = 6), respectively. On day 2, excretion of the metabolites decreased by one order of magnitude followed by a slower decrease on day 8. Regarding the possible formation of AcABPC from ABPC, N-acetylation of the amino group at the biphenyl moiety prior to that at cysteine appears to be very unlikely. Thus, the structure of AcABPC indicates the involvement of N-acetyl-4-biphenylnitrenium ion (AcBPN) and/or its reactive ester precursors in in vivo reactions with GSH and protein-bound cysteine. ABPC in globin might become an alternative biomarker of the dose of toxicologically relevant metabolic intermediates of 4-ABP.

Název v anglickém jazyce

New aminobiphenylcysteine derivatives in globin and urine of rats dosed with 4-aminobiphenyl, a tobacco smoke carcinogen

Popis výsledku anglicky

The 4-biphenylnitrenium ion (BPN), a reactive metabolic intermediate of the tobacco smoke carcinogen 4-aminobiphenyl (4-ABP), can react with nucleophilic sulfanyl groups in glutathione (GSH) as well as in proteins. The main site of attack of these S-nucleophiles was predicted using simple orientational rules of aromatic nucleophilic substitution. Thereafter, a series of presumptive 4-ABP metabolites and adducts with cysteine were synthesized, namely, S-(4-amino-3-biphenyl)cysteine (ABPC), N-acetyl-S-(4-amino-3-biphenyl)cysteine (4-amino-3-biphenylmercapturic acid, ABPMA), S-(4-acetamido-3-biphenyl)cysteine (AcABPC), and N-acetyl-S-(4-acetami-do-3-biphenyl)cysteine (4-acetamido-3-biphenylmercapturic acid, AcABP-MA). Then, globin and urine of rats dosed with a single ip dose of 4-ABP (27 mg/kg b.w.) was analyzed by HPLC-ESI-MS2. ABPC was identified in acid-hydrolyzed globin at levels of 3.52 +/- 0.50, 2.74 +/- 0.51, and 1.25 +/- 0.12 nmol/g globin (mean +/- S.D.; n = 6) on days 1, 3, and 8 after dosing, respectively. In the urine collected on day 1 (0-24 h) after dosing, excretion of ABPMA, AcABPMA, and AcABPC amounted to 1.97 +/- 0.88, 3.09 +/- 0.75, and 3.69 +/- 1.49 nmol/kg b.w. (mean +/- S.D.; n = 6), respectively. On day 2, excretion of the metabolites decreased by one order of magnitude followed by a slower decrease on day 8. Regarding the possible formation of AcABPC from ABPC, N-acetylation of the amino group at the biphenyl moiety prior to that at cysteine appears to be very unlikely. Thus, the structure of AcABPC indicates the involvement of N-acetyl-4-biphenylnitrenium ion (AcBPN) and/or its reactive ester precursors in in vivo reactions with GSH and protein-bound cysteine. ABPC in globin might become an alternative biomarker of the dose of toxicologically relevant metabolic intermediates of 4-ABP.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30304 - Public and environmental health

Projekt

<a href="/cs/project/NV19-09-00378" target="_blank" >NV19-09-00378: Štěpné produkty proteinových aduktů v moči jako nový typ biomarkerů v preventivní medicíně</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Chemical Research in Toxicology

ISSN

0893-228X

e-ISSN

1520-5010

Svazek periodika

36

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

430-437

Kód UT WoS článku

000943549900001

EID výsledku v databázi Scopus

2-s2.0-85149361320