The impact of chemotherapeutic drugs on the CYP1A1-catalysed metabolism of the environmental carcinogen benzo [a] pyrene: Effects in human colorectal HCT116 TP53( / ), TP53( /-) and TP53(-/-) cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F18%3A10375481" target="_blank" >RIV/00216208:11310/18:10375481 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1016/j.tox.2018.02.006" target="_blank" >http://dx.doi.org/10.1016/j.tox.2018.02.006</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.tox.2018.02.006" target="_blank" >10.1016/j.tox.2018.02.006</a>
Alternative languages
Result language
angličtina
Original language name
The impact of chemotherapeutic drugs on the CYP1A1-catalysed metabolism of the environmental carcinogen benzo [a] pyrene: Effects in human colorectal HCT116 TP53( / ), TP53( /-) and TP53(-/-) cells
Original language description
Polycyclic aromatic hydrocarbons such as benzo[a]pyrene (BaP) can induce cytochrome P450 1A1 (CYP1A1) via a p53-dependent mechanism. The effect of different p53-activating chemotherapeutic drugs on CYP1A1 expression, and the resultant effect on BaP metabolism, was investigated in a panel of isogenic human colorectal HCT116 cells with differing TP53 status. Cells that were TP53(+ / +), TP53(+ / -) or TP53(- / -) were treated for up to 48 h with 60 mu M cisplatin, 50 mu M etoposide or 5 mu M ellipticine, each of which caused high p53 induction at moderate cytotoxicity (60-80% cell viability). We found that etoposide and ellipticine induced CYP1A1 in TP53(+ / +) cells but not in TP53(- / -) cells, demonstrating that the mechanism of CYP1A1 induction is p53 dependent; cisplatin had no such effect. Co-incubation experiments with the drugs and 2.5 mu M BaP showed that: (i) etoposide increased CYP1A1 expression in TP53(+ / +) cells, and to a lesser extent in TP53(- / -) cells, compared to cells treated with BaP alone; (ii) ellipticine decreased CYP1A1 expression in TP53(+/+) cells in BaP co-incubations; and (iii) cisplatin did not affect BaP-mediated CYP1A1 expression. Further, whereas cisplatin and etoposide had virtually no influence on CYP1A1-catalysed BaP metabolism, ellipticine treatment strongly inhibited BaP bioactivation. Our results indicate that the underlying mechanisms whereby etoposide and ellipticine regulate CYP1A1 expression must be different and may not be linked to p53 activation alone. These results could be relevant for smokers, who are exposed to increased levels of BaP, when prescribing chemotherapeutic drugs. Beside gene-environment interactions, more considerations should be given to potential drug-environment interactions during chemotherapy.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/GA17-12816S" target="_blank" >GA17-12816S: Construction of modified apoferritin nanocarriers bearing anticancer drugs and study of mechanisms enhancing their efficiency in anticancer therapy</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Toxicology
ISSN
0300-483X
e-ISSN
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Volume of the periodical
398-399
Issue of the periodical within the volume
April 2018
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
12
Pages from-to
1-12
UT code for WoS article
000430995300001
EID of the result in the Scopus database
2-s2.0-85042428818