New aminobiphenylcysteine derivatives in globin and urine of rats dosed with 4-aminobiphenyl, a tobacco smoke carcinogen
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
New aminobiphenylcysteine derivatives in globin and urine of rats dosed with 4-aminobiphenyl, a tobacco smoke carcinogen
Original language description
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.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30304 - Public and environmental health
Result continuities
Project
<a href="/en/project/NV19-09-00378" target="_blank" >NV19-09-00378: Hydrolytic cleavage products of protein adducts in urine as a new type of biomarkers in preventive medicine</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Chemical Research in Toxicology
ISSN
0893-228X
e-ISSN
1520-5010
Volume of the periodical
36
Issue of the periodical within the volume
3
Country of publishing house
US - UNITED STATES
Number of pages
8
Pages from-to
430-437
UT code for WoS article
000943549900001
EID of the result in the Scopus database
2-s2.0-85149361320