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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/GA17-12816S" target="_blank" >GA17-12816S: Konstrukce modifikovaných apoferitinových nanočástic s protinádorovými léčivy a studium mechanismů potencujících jejich efektivitu v terapii</a><br>

Návaznosti

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

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Toxicology

ISSN

0300-483X

e-ISSN

—

Svazek periodika

398-399

Číslo periodika v rámci svazku

April 2018

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

12

Strana od-do

1-12

Kód UT WoS článku

000430995300001

EID výsledku v databázi Scopus

2-s2.0-85042428818