Impact of genetic modulation of SULT1A enzymes on DNA adduct formation by aristolochic acids and 3-nitrobenzanthrone

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F17%3A10328753" target="_blank" >RIV/00216208:11310/17:10328753 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1007/s00204-016-1808-6" target="_blank" >http://dx.doi.org/10.1007/s00204-016-1808-6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00204-016-1808-6" target="_blank" >10.1007/s00204-016-1808-6</a>

Result language

angličtina

Original language name

Impact of genetic modulation of SULT1A enzymes on DNA adduct formation by aristolochic acids and 3-nitrobenzanthrone

Original language description

Exposure to aristolochic acid (AA) causes aristolochic acid nephropathy (AAN) and Balkan endemic nephropathy (BEN). Conflicting results have been found for the role of human sulfotransferase 1A1 (SULT1A1) contributing to the metabolic activation of aristolochic acid I (AAI) in vitro. We evaluated the role of human SULT1A1 in AA bioactivation in vivo after treatment of transgenic mice carrying a functional human SULT1A1 - SULT1A2 gene cluster (i.e. hSULT1A1/2 mice) and Sult1a1(- /-) mice with AAI and aristolochic acid II (AAII). Both compounds formed characteristic DNA adducts in the intact mouse and in cytosolic incubations in vitro. However, we did not find differences in AAI-/AAII-DNA adduct levels between hSULT1A1/2 and wild-type (WT) mice in all tissues analysed including kidney and liver despite strong enhancement of sulfotransferase activity in both kidney and liver of hSULT1A1/2 mice relative to WT, kidney and liver being major organs involved in AA metabolism. In contrast, DNA adduct formation was strongly increased in hSULT1A1/2 mice compared to WT after treatment with 3-nitrobenzanthrone (3-NBA), another carcinogenic aromatic nitro compound where human SULT1A1/2 is known to contribute to genotoxicity. We found no differences in AI-/AAII-DNA adduct formation in Sult1a1(- /-) and WT mice in vivo. Using renal and hepatic cytosolic fractions of hSULT1A1/2 Sult1a1(- /-) and WT mice, we investigated AAI-DNA adduct formation in vitro but failed to find a contribution of human SULT1A1/2 or murine Sult1a1 to AAI bioactivation. Our results indicate that sulfo-conjugation catalysed by human SULT1A1 does not play a role in the activation pathways of AAI and AAII in vivo, but is important in 3-NBA bioactivation.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/GA14-18344S" target="_blank" >GA14-18344S: Development of nanoparticle-based cytostatics and enzymes for enhanced chemotherapy of human neuroblastomas and study of mechanisms of their action</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

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

Name of the periodical

Archives of Toxicology

ISSN

0340-5761

e-ISSN

—

Volume of the periodical

91

Issue of the periodical within the volume

4

Country of publishing house

DE - GERMANY

Number of pages

19

Pages from-to

1957-1975

UT code for WoS article

000398819200031

EID of the result in the Scopus database

2-s2.0-84983420827