Multiple resistance to carcinogens and xenobiotics: P-glycoproteins as universal detoxifiers

Autoren

Thomas Efferth
Manfred Volm

DOI

10.1007/s00204-017-1938-5

eISSN

1432-0738

ISSN

0340-5761

Ausgabe der Veröffentlichung

7

Zeitschrift

Archives of Toxicology

Sprache

en

Online publication date

2017

Paginierung

2515 - 2538

Datum der Veröffentlichung

2017

Status

Published

Herausgeber

Springer Science and Business Media LLC

Herausgeber URL

http://dx.doi.org/10.1007/s00204-017-1938-5

Datum der Datenerfassung

2023

Titel

Multiple resistance to carcinogens and xenobiotics: P-glycoproteins as universal detoxifiers

Ausgabe der Zeitschrift

91

Data source: Crossref

Abstract

The detoxification of toxic substances is of general relevance in all biological systems. The plethora of exogenous xenobiotic compounds and endogenous toxic metabolic products explains the evolutionary pressure of all organisms to develop molecular mechanisms to detoxify and excrete harmful substances from the body. P-glycoprotein and other members of the ATP-binding cassette (ABC) transporter family extrude innumerous chemical compounds out of cells. Their specific expression in diverse biological contexts cause different phenotypes: (1) multidrug resistance (MDR) and thus failure of cancer chemotherapy, (2) avoidance of accumulation of carcinogens and prevention of carcinogenesis in healthy tissues, (3) absorption, distribution, metabolization and excretion (ADME) of pharmacological drugs in human patients, (4) protection from environmental toxins in aquatic organisms (multi-xenobiotic resistance, MXR). Hence ABC-transporters may have opposing effects for organismic health reaching from harmful in MDR of tumors to beneficial for maintenance of health in MXR. While their inhibition by specific inhibitors may improve treatment success in oncology and avoid carcinogenesis, blocking of ABC-transporter-driven efflux by environmental pollutants leads to ecotoxicological consequences in marine biotopes. Poisoned seafood may enter the food-chain and cause intoxications in human beings. As exemplified with ABC-transporters, joining forces in interdisciplinary research may, therefore, be a wise strategy to fight problems in human medicine and environmental sciences.

Addresses

Department of Pharmaceutical Biology, Johannes Gutenberg University, Mainz, Germany. efferth@uni-mainz.de.

Autoren

Thomas Efferth
Thomas Efferth
Manfred Volm

DOI

10.1007/s00204-017-1938-5

eISSN

1432-0738

Externe Identifier

PubMed Identifier: 28175954

Open access

false

ISSN

0340-5761

Ausgabe der Veröffentlichung

7

Zeitschrift

Archives of toxicology

Schlüsselwörter

Humans
ATP-Binding Cassette Transporters
Xenobiotics
Environmental Pollutants
Carcinogens
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Ecotoxicology
Inactivation, Metabolic
ATP Binding Cassette Transporter, Subfamily B, Member 1

Sprache

eng

Medium

Print-Electronic

Online publication date

2017

Paginierung

2515 - 2538

Datum der Veröffentlichung

2017

Status

Published

Datum der Datenerfassung

2017

Titel

Multiple resistance to carcinogens and xenobiotics: P-glycoproteins as universal detoxifiers.

Sub types

Review
Journal Article

Ausgabe der Zeitschrift

91

Data source: Europe PubMed Central

Abstract

The detoxification of toxic substances is of general relevance in all biological systems. The plethora of exogenous xenobiotic compounds and endogenous toxic metabolic products explains the evolutionary pressure of all organisms to develop molecular mechanisms to detoxify and excrete harmful substances from the body. P-glycoprotein and other members of the ATP-binding cassette (ABC) transporter family extrude innumerous chemical compounds out of cells. Their specific expression in diverse biological contexts cause different phenotypes: (1) multidrug resistance (MDR) and thus failure of cancer chemotherapy, (2) avoidance of accumulation of carcinogens and prevention of carcinogenesis in healthy tissues, (3) absorption, distribution, metabolization and excretion (ADME) of pharmacological drugs in human patients, (4) protection from environmental toxins in aquatic organisms (multi-xenobiotic resistance, MXR). Hence ABC-transporters may have opposing effects for organismic health reaching from harmful in MDR of tumors to beneficial for maintenance of health in MXR. While their inhibition by specific inhibitors may improve treatment success in oncology and avoid carcinogenesis, blocking of ABC-transporter-driven efflux by environmental pollutants leads to ecotoxicological consequences in marine biotopes. Poisoned seafood may enter the food-chain and cause intoxications in human beings. As exemplified with ABC-transporters, joining forces in interdisciplinary research may, therefore, be a wise strategy to fight problems in human medicine and environmental sciences.

Date of acceptance

2017

Autoren

Thomas Efferth
Manfred Volm

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/28175954

DOI

10.1007/s00204-017-1938-5

eISSN

1432-0738

Ausgabe der Veröffentlichung

7

Zeitschrift

Arch Toxicol

Schlüsselwörter

ABC-transporter
Cancer
Carcinogenesis ecotoxicology
Multi-drug resistance
Multi-xenobiotic resistance
ATP Binding Cassette Transporter, Subfamily B, Member 1
ATP-Binding Cassette Transporters
Carcinogens
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Ecotoxicology
Environmental Pollutants
Humans
Inactivation, Metabolic
Xenobiotics

Sprache

eng

Country

Germany

Paginierung

2515 - 2538

PII

10.1007/s00204-017-1938-5

Datum der Veröffentlichung

2017

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2018

Titel

Multiple resistance to carcinogens and xenobiotics: P-glycoproteins as universal detoxifiers.

Sub types

Journal Article
Review

Ausgabe der Zeitschrift

91

Data source: PubMed

Multiple resistance to carcinogens and xenobiotics: P-glycoproteins as universal detoxifiers

Tools